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{{Short description|Molecule that carries genetic information}}
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[[File:DNA Structure+Key+Labelled.pn NoBB.png|thumb|right|upright=1.33|The structure of the DNA [[double helix]] (type [[B-DNA]]). The [[atom]]s in the structure are colour-coded by [[Chemical element|element]] and the detailed structures of two [[base pair]]s are shown in the bottom right.]][[File:Phosphate backbone.jpg|thumb|Simplified diagram]]
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'''Deoxyribonucleic acid''' ({{IPAc-en|audio=en-us-Deoxyribonucleic acid.ogg|d|iː|ˈ|ɒ|k|s|ᵻ|ˌ|r|aɪ|b|oʊ|nj|uː|ˌ|k|l|iː|ᵻ|k|,_|-|ˌ|k|l|eɪ|-}};<ref>{{MerriamWebsterDictionary|deoxyribonucleic acid}}</ref> '''DNA''') is a [[polymer]] composed of two [[polynucleotide]] chains that coil around each other to form a [[Nucleic acid double helix|double helix]]. The polymer carries [[genetics|genetic]] instructions for the development, functioning, growth and [[reproduction]] of all known [[organism]]s and many [[virus]]es. DNA and [[ribonucleic acid]] (RNA) are [[nucleic acid]]s. Alongside [[protein]]s, [[lipids]] and complex carbohydrates ([[polysaccharide]]s), nucleic acids are one of the four major types of [[macromolecule]]s that are essential for all known forms of [[life]].
The two DNA strands are known as polynucleotides as they are composed of simpler [[monomer]]ic units called [[nucleotide]]s.<ref>{{Cite book |vauthors= Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P |title= Molecular Biology of the Cell |edition= 6th |publisher= Garland |year= 2014 |url= http://www.garlandscience.com/product/isbn/9780815344322 |page= Chapter 4: DNA, Chromosomes and Genomes |isbn= 978-0-8153-4432-2 |url-status=live |archive-url= https://web.archive.org/web/20140714210549/http://www.garlandscience.com/product/isbn/9780815344322 |archive-date= 14 July 2014 |df= dmy-all }}</ref><ref>{{cite web | vauthors = Purcell A |title=DNA |url=http://basicbiology.net/micro/genetics/dna|website=Basic Biology |url-status=live |archive-url=https://web.archive.org/web/20170105045651/http://basicbiology.net/micro/genetics/dna/ |archive-date=5 January 2017}}</ref> Each nucleotide is composed of one of four [[nitrogenous base|nitrogen-containing]] [[nucleobase]]s ([[cytosine]] [C], [[guanine]] [G], [[adenine]] [A] or [[thymine]] [T]), a [[monosaccharide|sugar]] called [[deoxyribose]], and a [[Organophosphate|phosphate group]]. The nucleotides are joined to one another in a chain by [[covalent bond]]s (known as the [[Phosphodiester bond|phosphodiester linkage]]) between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating [[backbone chain|sugar-phosphate backbone]]. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to [[base pair]]ing rules (A with T and C with G), with [[hydrogen bond]]s to make double-stranded DNA. The complementary nitrogenous bases are divided into two groups, the single-ringed [[pyrimidine]]s and the double-ringed [[purine]]s. In DNA, the pyrimidines are thymine and cytosine; the purines are adenine and guanine.
Both strands of double-stranded DNA store the same [[Central dogma of molecular biology#Biological sequence information|biological information]]. This information is [[DNA replication|replicated]] when the two strands separate. A large part of DNA (more than 98% for humans) is [[non-coding DNA|non-coding]], meaning that these sections do not serve as patterns for [[Primary protein structure|protein sequences]]. The two strands of DNA run in opposite directions to each other and are thus [[antiparallel (biochemistry)|antiparallel]]. Attached to each sugar is one of four types of nucleobases (or ''bases''). It is the [[Nucleic acid sequence|sequence]] of these four nucleobases along the backbone that encodes genetic information. [[RNA]] strands are created using DNA strands as a template in a process called [[transcription (genetics)|transcription]], where DNA bases are exchanged for their corresponding bases except in the case of thymine (T), for which RNA substitutes [[uracil]] (U).<ref>{{Cite web|url=https://www.genome.gov/genetics-glossary/Uracil|title=Uracil|website=Genome.gov|language=en|access-date=21 November 2019}}</ref> Under the [[genetic code]], these RNA strands specify the sequence of [[amino acid]]s within proteins in a process called [[translation (genetics)|translation]].
Within eukaryotic cells, DNA is organized into long structures called [[chromosome]]s. Before typical [[cell division]], these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. [[Eukaryote|Eukaryotic organisms]] ([[animal]]s, [[plant]]s, [[Fungus|fungi]] and [[protist]]s) store most of their DNA inside the [[cell nucleus]] as [[nuclear DNA]], and some in the [[mitochondrion|mitochondria]] as [[mitochondrial DNA]] or in [[chloroplast]]s as [[chloroplast DNA]].<ref>{{cite book | vauthors = Russell P | title= iGenetics |url= https://archive.org/details/igenetics0000russ_v6o1 |url-access= registration |publisher= Benjamin Cummings |location= New York |year= 2001 |isbn= 0-8053-4553-1}}</ref> In contrast, [[prokaryote]]s ([[bacteria]] and [[archaea]]) store their DNA only in the [[cytoplasm]], in [[circular chromosome]]s. Within eukaryotic chromosomes, [[chromatin]] proteins, such as [[histone]]s, compact and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.
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== Properties ==
[[File:DNA chemical structure.svg|thumb|upright=1.35|Chemical structure of DNA; [[hydrogen bond]]s shown as dotted lines. Each end of the double helix has an exposed [[Directionality (molecular biology)#5′-end|5']] phosphate on one strand and an exposed [[Directionality (molecular biology)#3′-end|3′]] hydroxyl group (—OH) on the other.]]
DNA is a long [[polymer]] made from repeating units called [[nucleotide]]s.<ref>{{cite book | vauthors = Saenger W |title= Principles of Nucleic Acid Structure |publisher= Springer-Verlag |location= New York |year= 1984 |isbn= 0-387-90762-9}}</ref><ref name="Alberts">{{cite book | vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Peter W | title = Molecular Biology of the Cell | edition = Fourth | publisher = Garland Science | year = 2002 | location = New York and London | isbn = 0-8153-3218-1 | oclc = 145080076 | url = https://www.ncbi.nlm.nih.gov/books/NBK21054/ | url-status=live | archive-url = https://web.archive.org/web/20161101022040/https://www.ncbi.nlm.nih.gov/books/NBK21054/ | archive-date = 1 November 2016 | df = dmy-all }}</ref> The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes.<ref>{{cite journal | vauthors = Irobalieva RN, Fogg JM, Catanese DJ, Catanese DJ, Sutthibutpong T, Chen M, Barker AK, Ludtke SJ, Harris SA, Schmid MF, Chiu W, Zechiedrich L | title = Structural diversity of supercoiled DNA | journal = Nature Communications | volume = 6 | pages = 8440 | date = October 2015 | pmid = 26455586 | pmc = 4608029 | doi = 10.1038/ncomms9440 | bibcode = 2015NatCo...6.8440I |issn=2041-1723 }}</ref> In all species it is composed of two helical chains, bound to each other by [[hydrogen bonds]]. Both chains are coiled around the same axis, and have the same [[Pitch (screw)|pitch]] of {{convert|34|Å|nm|lk=on}}. The pair of chains have a radius of {{cvt|10|Å|nm}}.<ref name="Watson-1953">{{cite journal | vauthors = Watson JD, Crick FH | title = Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid | journal = Nature | volume = 171 | issue = 4356 | pages = 737–38 | date = April 1953 | pmid = 13054692 | doi = 10.1038/171737a0 | url = http://www.nature.com/nature/dna50/watsoncrick.pdf | bibcode = 1953Natur.171..737W | s2cid = 4253007 | url-status=live | archive-url = https://web.archive.org/web/20070204110320/http://www.nature.com/nature/dna50/watsoncrick.pdf | archive-date = 4 February 2007 | df = dmy-all |issn=0028-0836 }}</ref> According to another study, when measured in a different solution, the DNA chain measured {{cvt|22|-|26|Å|nm}} wide, and one nucleotide unit measured {{cvt|3.3|Å|nm}} long.<ref>{{cite journal | vauthors = Mandelkern M, Elias JG, Eden D, Crothers DM | title = The dimensions of DNA in solution | journal = Journal of Molecular Biology | volume = 152 | issue = 1 | pages = 153–61 | date = October 1981 | pmid = 7338906 | doi = 10.1016/0022-2836(81)90099-1|issn=0022-2836 }}</ref> The buoyant density of most DNA is 1.7g/cm<sup>3</sup>.<ref>{{cite journal |last1=Arrighi |first1=Frances E. |last2=Mandel |first2=Manley |last3=Bergendahl |first3=Janet |last4=Hsu |first4=T. C. |title=Buoyant densities of DNA of mammals |journal=Biochemical Genetics |date=June 1970 |volume=4 |issue=3 |pages=367–376 |doi=10.1007/BF00485753|pmid=4991030 |s2cid=27950750 |issn=0006-2928 }}</ref>
DNA does not usually exist as a single strand, but instead as a pair of strands that are held tightly together.<ref name="Watson-1953" /><ref name=berg>{{cite book | vauthors = Berg J, Tymoczko J, Stryer L | date = 2002 | title = Biochemistry | publisher = W.H. Freeman and Company | isbn = 0-7167-4955-6 }}</ref> These two long strands coil around each other, in the shape of a [[double helix]]. The nucleotide contains both a segment of the [[Backbone chain|backbone]] of the molecule (which holds the chain together) and a [[nucleobase]] (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a [[nucleoside]], and a base linked to a sugar and to one or more phosphate groups is called a [[nucleotide]]. A [[biopolymer]] comprising multiple linked nucleotides (as in DNA) is called a [[polynucleotide]].<ref name="IUPAC">{{cite journal | author = IUPAC-IUB Commission on Biochemical Nomenclature (CBN) | title = Abbreviations and Symbols for Nucleic Acids, Polynucleotides and their Constituents. Recommendations 1970 | journal = The Biochemical Journal | volume = 120 | issue = 3 | pages = 449–54 | date = December 1970 | pmid = 5499957 | pmc = 1179624 | doi = 10.1042/bj1200449 | url = http://www.chem.qmul.ac.uk/iupac/misc/naabb.html | archive-url = https://web.archive.org/web/20070205191106/http://www.chem.qmul.ac.uk/iupac/misc/naabb.html | url-status=dead | archive-date = 5 February 2007 |issn=0306-3283 }}</ref>
The backbone of the DNA strand is made from alternating [[phosphate]] and [[carbohydrate|sugar]] groups.<ref name=Ghosh>{{cite journal | vauthors = Ghosh A, Bansal M | title = A glossary of DNA structures from A to Z | journal = Acta Crystallographica Section D | volume = 59 | issue = Pt 4 | pages = 620–26 | date = April 2003 | pmid = 12657780 | doi = 10.1107/S0907444903003251| bibcode = 2003AcCrD..59..620G |issn=0907-4449 }}</ref> The sugar in DNA is [[deoxyribose|2-deoxyribose]], which is a [[pentose]] (five-[[carbon]]) sugar. The sugars are joined by phosphate groups that form [[phosphodiester bond]]s between the third and fifth carbon [[atom]]s of adjacent sugar rings. These are known as the [[Directionality (molecular biology)#3′-end|3′-end]] (three prime end), and [[Directionality (molecular biology)#5′-end|5′-end]] (five prime end) carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a [[glycosidic bond]].<ref name="berg" />
Therefore, any DNA strand normally has one end at which there is a phosphate group attached to the 5′ carbon of a ribose (the 5′ phosphoryl) and another end at which there is a free hydroxyl group attached to the 3′ carbon of a ribose (the 3′ hydroxyl). The orientation of the 3′ and 5′ carbons along the sugar-phosphate backbone confers [[directionality (molecular biology)|directionality]] (sometimes called polarity) to each DNA strand. In a [[nucleic acid double helix]], the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are [[Antiparallel (biochemistry)|antiparallel]]. The asymmetric ends of DNA strands are said to have a directionality of five prime end (5′ ), and three prime end (3′), with the 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and [[RNA]] is the sugar, with the 2-deoxyribose in DNA being replaced by the related pentose sugar [[ribose]] in RNA.<ref name="berg" />
[[File:DNA animation.gif|thumb|upright|A section of DNA. The bases lie horizontally between the two spiraling strands<ref>{{Cite web| vauthors = Edwards KJ, Brown DG, Spink N, Skelly JV, Neidle S |title=RCSB PDB – 1D65: Molecular structure of the B-DNA dodecamer d(CGCAAATTTGCG)2. An examination of propeller twist and minor-groove water structure at 2.2 A resolution.|url=https://www.rcsb.org/structure/1D65|access-date=2023-03-27|website=www.rcsb.org|language=en-US}}</ref> ([[:File:DNA orbit animated.gif|animated version]]).]]
The DNA double helix is stabilized primarily by two forces: [[hydrogen bond]]s between nucleotides and [[Stacking (chemistry)|base-stacking]] interactions among [[aromatic]] nucleobases.<ref name="Yakovchuk2006">{{cite journal | vauthors = Yakovchuk P, Protozanova E, Frank-Kamenetskii MD | title = Base-stacking and base-pairing contributions into thermal stability of the DNA double helix | journal = Nucleic Acids Research | volume = 34 | issue = 2 | pages = 564–74 | year = 2006 | pmid = 16449200 | pmc = 1360284 | doi = 10.1093/nar/gkj454 |issn=0305-1048 }}</ref> The four bases found in DNA are [[adenine]] ({{mono|A}}), [[cytosine]] ({{mono|C}}), [[guanine]] ({{mono|G}}) and [[thymine]] ({{mono|T}}). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for [[adenosine monophosphate]]. Adenine pairs with thymine and guanine pairs with cytosine, forming {{mono|A-T}} and {{mono|G-C}} [[base pair]]s.<ref>{{cite book | vauthors = Tropp BE | title = Molecular Biology | edition = 4th | year = 2012 | publisher = Jones and Barlett Learning | location = Sudbury, Mass. | isbn = 978-0-7637-8663-2 }}</ref><ref>{{cite web | url = https://www.mun.ca/biology/scarr/Watson-Crick_Model.html | title = Watson-Crick Structure of DNA | year = 1953 | vauthors = Carr S | publisher = Memorial University of Newfoundland | access-date=13 July 2016 | url-status=live | archive-url = https://web.archive.org/web/20160719095721/http://www.mun.ca/biology/scarr/Watson-Crick_Model.html | archive-date = 19 July 2016 | df = dmy-all }}</ref>
=== Nucleobase classification ===
The nucleobases are classified into two types: the [[purine]]s, {{mono|A}} and {{mono|G}}, which are fused five- and six-membered [[heterocyclic compound]]s, and the [[pyrimidine]]s, the six-membered rings {{mono|C}} and {{mono|T}}.<ref name=berg /> A fifth pyrimidine nucleobase, [[uracil]] ({{mono|U}}), usually takes the place of thymine in RNA and differs from thymine by lacking a [[methyl group]] on its ring. In addition to RNA and DNA, many artificial [[nucleic acid analogue]]s have been created to study the properties of nucleic acids, or for use in biotechnology.<ref>{{cite journal | vauthors = Verma S, Eckstein F | title = Modified oligonucleotides: synthesis and strategy for users | journal = Annual Review of Biochemistry | volume = 67 | pages = 99–134 | year = 1998 | pmid = 9759484 |issn=0066-4154 | doi = 10.1146/annurev.biochem.67.1.99 | doi-access = free }}</ref>
=== Non-canonical bases ===
Modified bases occur in DNA. The first of these recognized was [[5-methylcytosine]], which was found in the [[genome]] of ''[[Mycobacterium tuberculosis]]'' in 1925.<ref name=Johnson1925>{{cite journal | vauthors = Johnson TB, Coghill RD | year = 1925 | title = Pyrimidines. CIII. The discovery of 5-methylcytosine in tuberculinic acid, the nucleic acid of the tubercle bacillus. | journal = Journal of the American Chemical Society | volume = 47 | pages = 2838–44 | doi=10.1021/ja01688a030|issn=0002-7863}}</ref> The reason for the presence of these noncanonical bases in bacterial viruses ([[bacteriophage]]s) is to avoid the [[restriction enzyme]]s present in bacteria. This enzyme system acts at least in part as a molecular immune system protecting bacteria from infection by viruses.<ref name="pmid27319741">{{cite journal |vauthors=Weigele P, Raleigh EA |title=Biosynthesis and Function of Modified Bases in Bacteria and Their Viruses |journal=Chemical Reviews |volume=116 |issue=20 |pages=12655–12687 |date=October 2016 |pmid=27319741 |doi=10.1021/acs.chemrev.6b00114 |doi-access=free |issn=0009-2665 }}</ref> Modifications of the bases cytosine and adenine, the more common and modified DNA bases, play vital roles in the [[epigenetics|epigenetic]] control of gene expression in plants and animals.<ref name="pmid30619465">{{cite journal |vauthors=Kumar S, Chinnusamy V, Mohapatra T |title=Epigenetics of Modified DNA Bases: 5-Methylcytosine and Beyond |journal=Frontiers in Genetics |volume=9 |pages=640 |date=2018 |pmid=30619465 |pmc=6305559 |doi=10.3389/fgene.2018.00640 |issn=1664-8021 |doi-access=free }}</ref>
A number of noncanonical bases are known to occur in DNA.<ref name="pmid28941008">{{cite journal | vauthors = Carell T, Kurz MQ, Müller M, Rossa M, Spada F | title = Non-canonical Bases in the Genome: The Regulatory Information Layer in DNA | journal = Angewandte Chemie | volume = 57 | issue = 16 | pages = 4296–4312 | date = April 2018 | pmid = 28941008 | doi = 10.1002/anie.201708228 }}</ref> Most of these are modifications of the canonical bases plus uracil.
* Modified '''Adenine'''
** N6-carbamoyl-methyladenine
** N6-methyadenine
* Modified '''Guanine'''
** 7-Deazaguanine
** 7-Methylguanine
* Modified '''Cytosine'''
** N4-Methylcytosine
** 5-Carboxylcytosine
** 5-Formylcytosine
** 5-Glycosylhydroxymethylcytosine
** 5-Hydroxycytosine
** 5-Methylcytosine
* Modified '''Thymidine'''
** α-Glutamythymidine
** α-Putrescinylthymine
* '''Uracil''' and modifications
** Base J
** Uracil
** 5-Dihydroxypentauracil
** 5-Hydroxymethyldeoxyuracil
* Others
** Deoxyarchaeosine
** 2,6-Diaminopurine (2-Aminoadenine)
=== Grooves ===
[[File:DNA-ligand-by-Abalone.png|thumb|DNA major and minor grooves. The latter is a binding site for the [[Hoechst stain]] dye 33258.]]
Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a [[binding site]]. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. The major groove is {{convert|22|Å|nm}} wide, while the minor groove is {{cvt|12|Å|nm}} in width.<ref>{{cite journal | vauthors = Wing R, Drew H, Takano T, Broka C, Tanaka S, Itakura K, Dickerson RE | title = Crystal structure analysis of a complete turn of B-DNA | journal = Nature | volume = 287 | issue = 5784 | pages = 755–58 | date = October 1980 | pmid = 7432492 | doi = 10.1038/287755a0 | bibcode = 1980Natur.287..755W | s2cid = 4315465 }}</ref> Due to the larger width of the major groove, the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as [[transcription factor]]s that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove.<ref name="Pabo1984">{{cite journal | vauthors = Pabo CO, Sauer RT | title = Protein-DNA recognition | journal = Annual Review of Biochemistry | volume = 53 | pages = 293–321 | year = 1984 | pmid = 6236744 | doi = 10.1146/annurev.bi.53.070184.001453 }}</ref> This situation varies in unusual conformations of DNA within the cell ''(see below)'', but the major and minor grooves are always named to reflect the differences in width that would be seen if the DNA was twisted back into the ordinary [[B-DNA|B form]].
=== Base pairing ===
{{further|Base pair}}
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<div style="border: none; width:282px;"><div class="thumbcaption">Top, a '''{{mono|GC}}''' base pair with three [[hydrogen bond]]s. Bottom, an '''{{mono|AT}}''' base pair with two hydrogen bonds. Non-covalent hydrogen bonds between the pairs are shown as dashed lines.</div></div></div>
In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called [[Complementarity (molecular biology)|complementary]] [[base pair]]ing. Purines form [[hydrogen bond]]s to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix (from six-carbon ring to six-carbon ring) is called a Watson-Crick base pair. DNA with high [[GC-content]] is more stable than DNA with low {{mono|GC}}-content. A [[Hoogsteen base pair]] (hydrogen bonding the 6-carbon ring to the 5-carbon ring) is a rare variation of base-pairing.<ref name="pmid23818176">{{cite journal |vauthors=Nikolova EN, Zhou H, Gottardo FL, Alvey HS, Kimsey IJ, Al-Hashimi HM |title=A historical account of Hoogsteen base-pairs in duplex DNA |journal=Biopolymers |volume=99 |issue=12 |pages=955–68 |year=2013 |pmid=23818176 |pmc=3844552 |doi=10.1002/bip.22334 }}</ref> As hydrogen bonds are not [[covalent bond|covalent]], they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can thus be pulled apart like a zipper, either by a mechanical force or high [[temperature]].<ref>{{cite journal | vauthors = Clausen-Schaumann H, Rief M, Tolksdorf C, Gaub HE | title = Mechanical stability of single DNA molecules | journal = Biophysical Journal | volume = 78 | issue = 4 | pages = 1997–2007 | date = April 2000 | pmid = 10733978 | pmc = 1300792 | doi = 10.1016/S0006-3495(00)76747-6 | bibcode = 2000BpJ....78.1997C }}</ref> As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in organisms.<ref name=Alberts />
{{Anchor|ssDNA}}
==== ssDNA vs. dsDNA ====
Most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double-stranded (dsDNA) structure is maintained largely by the intrastrand base stacking interactions, which are strongest for {{mono|G,C}} stacks. The two strands can come apart—a process known as melting—to form two single-stranded DNA (ssDNA) molecules. Melting occurs at high temperatures, low salt and high [[pH]] (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).
The stability of the dsDNA form depends not only on the {{mono|GC}}-content (% {{mono|G,C}} basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the [[DNA melting|melting temperature]] (also called ''T<sub>m</sub>'' value), which is the temperature at which 50% of the double-strand molecules are converted to single-strand molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of {{mono|GC}} base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high {{mono|GC}}-content have more strongly interacting strands, while short helices with high {{mono|AT}} content have more weakly interacting strands.<ref>{{cite journal | vauthors = Chalikian TV, Völker J, Plum GE, Breslauer KJ | title = A more unified picture for the thermodynamics of nucleic acid duplex melting: a characterization by calorimetric and volumetric techniques | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 14 | pages = 7853–58 | date = July 1999 | pmid = 10393911 | pmc = 22151 | doi = 10.1073/pnas.96.14.7853 | bibcode = 1999PNAS...96.7853C | doi-access = free }}</ref> In biology, parts of the DNA double helix that need to separate easily, such as the {{mono|TATAAT}} [[Pribnow box]] in some [[promoter (biology)|promoters]], tend to have a high {{mono|AT}} content, making the strands easier to pull apart.<ref>{{cite journal | vauthors = deHaseth PL, Helmann JD | title = Open complex formation by Escherichia coli RNA polymerase: the mechanism of polymerase-induced strand separation of double helical DNA | journal = Molecular Microbiology | volume = 16 | issue = 5 | pages = 817–24 | date = June 1995 | pmid = 7476180 | doi = 10.1111/j.1365-2958.1995.tb02309.x | s2cid = 24479358 }}</ref>
In the laboratory, the strength of this interaction can be measured by finding the melting temperature ''T<sub>m</sub>'' necessary to break half of the hydrogen bonds. When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others.<ref>{{cite journal | vauthors = Isaksson J, Acharya S, Barman J, Cheruku P, Chattopadhyaya J | title = Single-stranded adenine-rich DNA and RNA retain structural characteristics of their respective double-stranded conformations and show directional differences in stacking pattern | journal = Biochemistry | volume = 43 | issue = 51 | pages = 15996–6010 | date = December 2004 | pmid = 15609994 | doi = 10.1021/bi048221v | url = http://www.boc.uu.se/boc14www/thesis/johan2005/Paper%20V/Paper%20V.pdf | url-status=live | archive-url = https://web.archive.org/web/20070610205112/http://www.boc.uu.se/boc14www/thesis/johan2005/Paper%20V/Paper%20V.pdf | archive-date = 10 June 2007 | df = dmy-all }}</ref>
=== Amount ===
[[File:Human karyotype with bands and sub-bands.png|thumb|Schematic [[karyotype|karyogram]] of a human. It shows 22 [[homologous chromosome]]s, both the female (XX) and male (XY) versions of the [[sex chromosome]] (bottom right), as well as the [[human mitochondrial genetics|mitochondrial genome]] (to scale at bottom left). The blue scale to the left of each chromosome pair (and the mitochondrial genome) shows its length in terms of millions of DNA [[base pair]]s.{{further|Karyotype}}]]
In humans, the total female [[diploid]] [[nuclear genome]] per cell extends for 6.37 Gigabase pairs (Gbp), is 208.23&nbsp;cm long and weighs 6.51 picograms (pg).<ref name="pmid30813969">{{cite journal| vauthors=Piovesan A, Pelleri MC, Antonaros F, Strippoli P, Caracausi M, Vitale L| title=On the length, weight and GC content of the human genome. | journal=BMC Res Notes | year= 2019 | volume= 12 | issue= 1 | pages= 106 | pmid=30813969 | doi=10.1186/s13104-019-4137-z | pmc=6391780 | doi-access=free }}</ref> Male values are 6.27 Gbp, 205.00&nbsp;cm, 6.41 pg.<ref name="pmid30813969"/> Each DNA polymer can contain hundreds of millions of nucleotides, such as in [[chromosome 1]]. Chromosome 1 is the largest human [[chromosome]] with approximately 220 million [[base pair]]s, and would be {{val|85|u=mm}} long if straightened.<ref name="Gregory_2006" />
In [[eukaryote]]s, in addition to [[nuclear DNA]], there is also [[mitochondrial DNA]] (mtDNA) which encodes certain proteins used by the mitochondria. The mtDNA is usually relatively small in comparison to the nuclear DNA. For example, the [[Human mitochondrial genetics|human mitochondrial DNA]] forms closed circular molecules, each of which contains 16,569<ref name="Anderson_1981">{{cite journal | vauthors = Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG | display-authors = 6 | title = Sequence and organization of the human mitochondrial genome | journal = Nature | volume = 290 | issue = 5806 | pages = 457–465 | date = April 1981 | pmid = 7219534 | doi = 10.1038/290457a0 | s2cid = 4355527 | bibcode = 1981Natur.290..457A }}</ref><ref>{{Cite web |url=http://chemistry.umeche.maine.edu/CHY431/MitoDNA.html |title=Untitled |access-date=2012-06-13 |archive-url=https://web.archive.org/web/20110813123936/http://chemistry.umeche.maine.edu/CHY431/MitoDNA.html |archive-date=2011-08-13 |url-status=dead }}</ref> DNA base pairs,<ref name=Satoh1991>{{cite journal | vauthors = Satoh M, Kuroiwa T | title = Organization of multiple nucleoids and DNA molecules in mitochondria of a human cell | journal = Experimental Cell Research | volume = 196 | issue = 1 | pages = 137–140 | date = September 1991 | pmid = 1715276 | doi = 10.1016/0014-4827(91)90467-9 }}</ref> with each such molecule normally containing a full set of the mitochondrial genes. Each human mitochondrion contains, on average, approximately 5 such mtDNA molecules.<ref name=Satoh1991/> Each human [[Cell (biology)|cell]] contains approximately 100 mitochondria, giving a total number of mtDNA molecules per human cell of approximately 500.<ref name=Satoh1991/> However, the amount of mitochondria per cell also varies by cell type, and an [[egg cell]] can contain 100,000 mitochondria, corresponding to up to 1,500,000 copies of the mitochondrial genome (constituting up to 90% of the DNA of the cell).<ref name="pmid28721182">{{cite journal | vauthors = Zhang D, Keilty D, Zhang ZF, Chian RC | title = Mitochondria in oocyte aging: current understanding | journal = Facts, Views & Vision in ObGyn | volume = 9 | issue = 1 | pages = 29–38 | date = March 2017 | pmid = 28721182 | pmc = 5506767 }}</ref>
=== Sense and antisense ===
{{further|Sense (molecular biology)}}
A [[DNA sequencing|DNA sequence]] is called a "sense" sequence if it is the same as that of a [[messenger RNA]] copy that is translated into protein.<ref>[http://www.chem.qmul.ac.uk/iubmb/newsletter/misc/DNA.html Designation of the two strands of DNA] {{Webarchive|url=https://web.archive.org/web/20080424015915/http://www.chem.qmul.ac.uk/iubmb/newsletter/misc/DNA.html |date=24 April 2008 }} JCBN/NC-IUB Newsletter 1989. Retrieved 7 May 2008</ref> The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear.<ref>{{cite journal | vauthors = Hüttenhofer A, Schattner P, Polacek N | title = Non-coding RNAs: hope or hype? | journal = Trends in Genetics | volume = 21 | issue = 5 | pages = 289–97 | date = May 2005 | pmid = 15851066 | doi = 10.1016/j.tig.2005.03.007 }}</ref> One proposal is that antisense RNAs are involved in regulating [[gene expression]] through RNA-RNA base pairing.<ref>{{cite journal | vauthors = Munroe SH | title = Diversity of antisense regulation in eukaryotes: multiple mechanisms, emerging patterns | journal = Journal of Cellular Biochemistry | volume = 93 | issue = 4 | pages = 664–71 | date = November 2004 | pmid = 15389973 | doi = 10.1002/jcb.20252 | s2cid = 23748148 }}</ref>
A few DNA sequences in prokaryotes and eukaryotes, and more in [[plasmid]]s and [[virus]]es, blur the distinction between sense and antisense strands by having [[overlapping gene]]s.<ref>{{cite journal | vauthors = Makalowska I, Lin CF, Makalowski W | title = Overlapping genes in vertebrate genomes | journal = Computational Biology and Chemistry | volume = 29 | issue = 1 | pages = 1–12 | date = February 2005 | pmid = 15680581 | doi = 10.1016/j.compbiolchem.2004.12.006 }}</ref> In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In [[bacteria]], this overlap may be involved in the regulation of gene transcription,<ref>{{cite journal | vauthors = Johnson ZI, Chisholm SW | title = Properties of overlapping genes are conserved across microbial genomes | journal = Genome Research | volume = 14 | issue = 11 | pages = 2268–72 | date = November 2004 | pmid = 15520290 | pmc = 525685 | doi = 10.1101/gr.2433104 }}</ref> while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.<ref>{{cite journal | vauthors = Lamb RA, Horvath CM | title = Diversity of coding strategies in influenza viruses | journal = Trends in Genetics | volume = 7 | issue = 8 | pages = 261–66 | date = August 1991 | pmid = 1771674 | doi = 10.1016/0168-9525(91)90326-L | pmc = 7173306 }}</ref>
=== Supercoiling ===
{{further|DNA supercoil}}
DNA can be twisted like a rope in a process called [[DNA supercoil]]ing. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound.<ref>{{cite journal | vauthors = Benham CJ, Mielke SP | s2cid = 1427671 | title = DNA mechanics | journal = Annual Review of Biomedical Engineering | volume = 7 | pages = 21–53 | year = 2005 | pmid = 16004565 | doi = 10.1146/annurev.bioeng.6.062403.132016 | url = http://pdfs.semanticscholar.org/ab63/d57290ebf9bc3536fd3f2257a2b509076fc1.pdf | archive-url = https://web.archive.org/web/20190301225243/http://pdfs.semanticscholar.org/ab63/d57290ebf9bc3536fd3f2257a2b509076fc1.pdf | url-status = dead | archive-date = 1 March 2019 }}</ref> If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by [[enzyme]]s called [[topoisomerase]]s.<ref name=Champoux>{{cite journal | vauthors = Champoux JJ | s2cid = 18144189 | title = DNA topoisomerases: structure, function, and mechanism | journal = Annual Review of Biochemistry | volume = 70 | pages = 369–413 | year = 2001 | pmid = 11395412 | doi = 10.1146/annurev.biochem.70.1.369 }}</ref> These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as [[transcription (genetics)|transcription]] and [[DNA replication]].<ref name=Wang>{{cite journal | vauthors = Wang JC | title = Cellular roles of DNA topoisomerases: a molecular perspective | journal = Nature Reviews Molecular Cell Biology | volume = 3 | issue = 6 | pages = 430–40 | date = June 2002 | pmid = 12042765 | doi = 10.1038/nrm831 | s2cid = 205496065 }}</ref>
=== Alternative DNA structures ===
{{further|Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid|Molecular models of DNA|DNA structure}}
[[File:Dnaconformations.png|thumb|right|From left to right, the structures of [[A-DNA|A]], [[B-DNA|B]] and [[Z-DNA]]]]
DNA exists in many possible [[Conformational isomerism|conformations]] that include [[A-DNA]], [[B-DNA]], and [[Z-DNA]] forms, although only B-DNA and Z-DNA have been directly observed in functional organisms.<ref name=Ghosh /> The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal [[ion]]s, and the presence of [[polyamine]]s in solution.<ref>{{cite journal | vauthors = Basu HS, Feuerstein BG, Zarling DA, Shafer RH, Marton LJ | title = Recognition of Z-RNA and Z-DNA determinants by polyamines in solution: experimental and theoretical studies | journal = Journal of Biomolecular Structure & Dynamics | volume = 6 | issue = 2 | pages = 299–309 | date = October 1988 | pmid = 2482766 | doi = 10.1080/07391102.1988.10507714 }}</ref>
The first published reports of A-DNA [[X-ray diffraction patterns]]—and also B-DNA—used analyses based on [[Patterson function]]s that provided only a limited amount of structural information for oriented fibers of DNA.<ref>
* {{cite journal |vauthors=Franklin RE, Gosling RG |title=The Structure of Sodium Thymonucleate Fibres I. The Influence of Water Content |journal=Acta Crystallogr |volume=6 |issue=8–9 |pages=673–77 |date=6 March 1953 |doi=10.1107/S0365110X53001939 |bibcode=1953AcCry...6..673F |url=http://journals.iucr.org/q/issues/1953/08-09/00/a00979/a00979.pdf |url-status=live |archive-url=https://web.archive.org/web/20160109043915/http://journals.iucr.org/q/issues/1953/08-09/00/a00979/a00979.pdf |archive-date=9 January 2016 |doi-access=free }}
* {{cite journal |vauthors=Franklin RE, Gosling RG |title=The structure of sodium thymonucleate fibres. II. The cylindrically symmetrical Patterson function |journal=Acta Crystallogr |volume=6 |issue=8–9 |pages=678–85 |year=1953|doi=10.1107/S0365110X53001940|bibcode=1953AcCry...6..678F |url=http://journals.iucr.org/q/issues/1953/08-09/00/a00980/a00980.pdf |archive-url=https://web.archive.org/web/20170629084321/http://journals.iucr.org/q/issues/1953/08-09/00/a00980/a00980.pdf |archive-date=2017-06-29 |url-status=live |doi-access=free }}</ref><ref name=NatFranGos>{{cite journal | vauthors = Franklin RE, Gosling RG | title = Molecular configuration in sodium thymonucleate | journal = Nature | volume = 171 | issue = 4356 | pages = 740–41 | date = April 1953 | pmid = 13054694 | doi = 10.1038/171740a0 | url = http://www.nature.com/nature/dna50/franklingosling.pdf | bibcode = 1953Natur.171..740F | s2cid = 4268222 | url-status=live | archive-url = https://web.archive.org/web/20110103160712/http://www.nature.com/nature/dna50/franklingosling.pdf | archive-date = 3 January 2011 | df = dmy-all }}</ref> An alternative analysis was proposed by Wilkins ''et al.'' in 1953 for the ''[[in vivo]]'' B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of [[Bessel function]]s.<ref name=NatWilk>{{cite journal | vauthors = Wilkins MH, Stokes AR, Wilson HR | title = Molecular structure of deoxypentose nucleic acids | journal = Nature | volume = 171 | issue = 4356 | pages = 738–40 | date = April 1953 | pmid = 13054693 | doi = 10.1038/171738a0 | url = http://www.nature.com/nature/dna50/wilkins.pdf | bibcode = 1953Natur.171..738W | s2cid = 4280080 | url-status=live | archive-url = https://web.archive.org/web/20110513234223/http://www.nature.com/nature/dna50/wilkins.pdf | archive-date = 13 May 2011 | df = dmy-all }}</ref> In the same journal, [[James Watson]] and [[Francis Crick]] presented their [[Molecular models of DNA|molecular modeling]] analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double helix.<ref name="Watson-1953" />
Although the ''B-DNA form'' is most common under the conditions found in cells,<ref>{{cite journal | vauthors = Leslie AG, Arnott S, Chandrasekaran R, Ratliff RL | title = Polymorphism of DNA double helices | journal = Journal of Molecular Biology | volume = 143 | issue = 1 | pages = 49–72 | date = October 1980 | pmid = 7441761 | doi = 10.1016/0022-2836(80)90124-2 }}</ref> it is not a well-defined conformation but a family of related DNA conformations<ref>{{cite journal|vauthors=Baianu IC|s2cid=189888972|year=1980|title=Structural Order and Partial Disorder in Biological systems|url=http://cogprints.org/3822/|journal=Bull. Math. Biol.|volume=42|issue=4|pages=137–41|doi=10.1007/BF02462372}}</ref> that occur at the high hydration levels present in cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular [[Paracrystalline|paracrystals]] with a significant degree of disorder.<ref>{{cite book | vauthors = Hosemann R, Bagchi RN | title = Direct analysis of diffraction by matter | publisher = North-Holland Publishers | location = Amsterdam&nbsp;– New York | year = 1962 }}</ref><ref>{{cite journal|vauthors=Baianu IC|title=X-ray scattering by partially disordered membrane systems|journal=Acta Crystallogr A|volume=34|issue=5|pages=751–53|year=1978|doi=10.1107/S0567739478001540|bibcode=1978AcCrA..34..751B|url=http://journals.iucr.org/a/issues/1978/05/00/a15615/a15615.pdf|access-date=29 August 2019|archive-date=14 March 2020|archive-url=https://web.archive.org/web/20200314050140/http://journals.iucr.org/a/issues/1978/05/00/a15615/a15615.pdf|url-status=dead}}</ref>
Compared to B-DNA, the A-DNA form is a wider [[Helix#Properties and types|right-handed]] spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes.<ref>{{cite journal | vauthors = Wahl MC, Sundaralingam M | title = Crystal structures of A-DNA duplexes | journal = Biopolymers | volume = 44 | issue = 1 | pages = 45–63 | year = 1997 | pmid = 9097733 | doi = 10.1002/(SICI)1097-0282(1997)44:1<45::AID-BIP4>3.0.CO;2-# }}</ref><ref>{{cite journal | vauthors = Lu XJ, Shakked Z, Olson WK | title = A-form conformational motifs in ligand-bound DNA structures | journal = Journal of Molecular Biology | volume = 300 | issue = 4 | pages = 819–40 | date = July 2000 | pmid = 10891271 | doi = 10.1006/jmbi.2000.3690 }}</ref> Segments of DNA where the bases have been chemically modified by [[methylation]] may undergo a larger change in conformation and adopt the [[Z-DNA|Z form]]. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form.<ref>{{cite journal | vauthors = Rothenburg S, Koch-Nolte F, Haag F | title = DNA methylation and Z-DNA formation as mediators of quantitative differences in the expression of alleles | journal = Immunological Reviews | volume = 184 | pages = 286–98 | date = December 2001 | pmid = 12086319 | doi = 10.1034/j.1600-065x.2001.1840125.x | s2cid = 20589136 }}</ref> These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.<ref>{{cite journal | vauthors = Oh DB, Kim YG, Rich A | title = Z-DNA-binding proteins can act as potent effectors of gene expression in vivo | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 26 | pages = 16666–71 | date = December 2002 | pmid = 12486233 | pmc = 139201 | doi = 10.1073/pnas.262672699 | bibcode = 2002PNAS...9916666O | doi-access = free }}</ref>
=== Alternative DNA chemistry ===
{{further|hypothetical types of biochemistry}}
For many years, [[Astrobiology|exobiologists]] have proposed the existence of a [[shadow biosphere]], a postulated microbial [[biosphere]] of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use [[Arsenic DNA|arsenic instead of phosphorus in DNA]]. A report in 2010 of the possibility in the [[bacterium]] [[GFAJ-1]] was announced,<ref name='arsenic extremophile'>{{cite news | vauthors = Palmer J |title=Arsenic-loving bacteria may help in hunt for alien life |date=2 December 2010 |url=https://www.bbc.co.uk/news/science-environment-11886943 |work=BBC News |access-date=2 December 2010 |url-status=live |archive-url=https://web.archive.org/web/20101203045804/http://www.bbc.co.uk/news/science-environment-11886943 |archive-date=3 December 2010 }}</ref><ref name="Space">{{cite news | vauthors = Bortman H |title=Arsenic-Eating Bacteria Opens New Possibilities for Alien Life |date=2 December 2010 |url=http://www.space.com/scienceastronomy/arsenic-bacteria-alien-life-101202.html |website=Space.com |access-date=2 December 2010 |url-status=live |archive-url=https://web.archive.org/web/20101204235915/http://www.space.com/scienceastronomy/arsenic-bacteria-alien-life-101202.html |archive-date=4 December 2010 }}</ref> though the research was disputed,<ref name="Space" /><ref>{{cite journal | vauthors = Katsnelson A |title=Arsenic-eating microbe may redefine chemistry of life |date=2 December 2010 |url=http://www.nature.com/news/2010/101202/full/news.2010.645.html |journal=Nature News |doi=10.1038/news.2010.645 |url-status=live |archive-url=https://web.archive.org/web/20120212155007/http://www.nature.com/news/2010/101202/full/news.2010.645.html |archive-date=12 February 2012 }}</ref> and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.<ref name="Nature">{{cite journal | vauthors = Cressey D |s2cid=87341731 |title='Arsenic-life' Bacterium Prefers Phosphorus after all |date=3 October 2012 |journal=Nature News |doi=10.1038/nature.2012.11520}}</ref>
=== Quadruplex structures ===
{{further|G-quadruplex}}
[[File:Parallel telomere quadruple.png|thumb|right|DNA quadruplex formed by [[telomere]] repeats. The looped conformation of the DNA backbone is very different from the typical DNA helix. The green spheres in the center represent potassium ions.<ref>{{Cite web|title=Structure and packing of human telomeric DNA|url=http://ndbserver.rutgers.edu/service/ndb/atlas/summary?searchTarget=UD0017|access-date=2023-05-18|website=ndbserver.rutgers.edu}}</ref>]]
At the ends of the linear chromosomes are specialized regions of DNA called [[telomere]]s. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme [[telomerase]], as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes.<ref name=Greider>{{cite journal | vauthors = Greider CW, Blackburn EH | title = Identification of a specific telomere terminal transferase activity in Tetrahymena extracts | journal = Cell | volume = 43 | issue = 2 Pt 1 | pages = 405–13 | date = December 1985 | pmid = 3907856 | doi = 10.1016/0092-8674(85)90170-9 | doi-access = free }}</ref> These specialized chromosome caps also help protect the DNA ends, and stop the [[DNA repair]] systems in the cell from treating them as damage to be corrected.<ref name=Nugent>{{cite journal | vauthors = Nugent CI, Lundblad V | title = The telomerase reverse transcriptase: components and regulation | journal = Genes & Development | volume = 12 | issue = 8 | pages = 1073–85 | date = April 1998 | pmid = 9553037 | doi = 10.1101/gad.12.8.1073 | doi-access = free }}</ref> In [[List of distinct cell types in the adult human body|human cells]], telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.<ref>{{cite journal | vauthors = Wright WE, Tesmer VM, Huffman KE, Levene SD, Shay JW | title = Normal human chromosomes have long G-rich telomeric overhangs at one end | journal = Genes & Development | volume = 11 | issue = 21 | pages = 2801–09 | date = November 1997 | pmid = 9353250 | pmc = 316649 | doi = 10.1101/gad.11.21.2801 }}</ref>
These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases, known as a [[guanine tetrad]], form a flat plate. These flat four-base units then stack on top of each other to form a stable [[G-quadruplex]] structure.<ref name=Burge>{{cite journal | vauthors = Burge S, Parkinson GN, Hazel P, Todd AK, Neidle S | title = Quadruplex DNA: sequence, topology and structure | journal = Nucleic Acids Research | volume = 34 | issue = 19 | pages = 5402–15 | year = 2006 | pmid = 17012276 | pmc = 1636468 | doi = 10.1093/nar/gkl655 }}</ref> These structures are stabilized by hydrogen bonding between the edges of the bases and [[chelation]] of a metal ion in the centre of each four-base unit.<ref>{{cite journal | vauthors = Parkinson GN, Lee MP, Neidle S | title = Crystal structure of parallel quadruplexes from human telomeric DNA | journal = Nature | volume = 417 | issue = 6891 | pages = 876–80 | date = June 2002 | pmid = 12050675 | doi = 10.1038/nature755 | bibcode = 2002Natur.417..876P | s2cid = 4422211 }}</ref> Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.
In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins.<ref>{{cite journal | vauthors = Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T | s2cid = 721901 | title = Mammalian telomeres end in a large duplex loop | journal = Cell | volume = 97 | issue = 4 | pages = 503–14 | date = May 1999 | pmid = 10338214 | doi = 10.1016/S0092-8674(00)80760-6 | citeseerx = 10.1.1.335.2649 }}</ref> At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This [[Triple-stranded DNA|triple-stranded]] structure is called a displacement loop or [[D-loop]].<ref name=Burge />
=== Branched DNA ===
{{further|Branched DNA|DNA nanotechnology}}
<div class="thumb tright" style="background:#f9f9f9; border:1px solid #ccc; margin:0.5em;">
{| border="0" cellpadding="2" cellspacing="0" style="width:200px; font-size:85%; border:1px solid #ccc; margin:0.3em;"
|[[File:Branch-dna-single.svg|95px]]
|[[File:Branch-DNA-multiple.svg|95px]]
|-
|align=center|Single branch
|align=center|Multiple branches
|}
<div style="border: none; width:200px;font-size: 90%;"><div class="thumbcaption">[[Branched DNA]] can form networks containing multiple branches.</div></div></div>
In DNA, [[DNA end#Frayed ends|fraying]] occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible.<ref>{{cite journal | vauthors = Seeman NC | title = DNA enables nanoscale control of the structure of matter | journal = Quarterly Reviews of Biophysics | volume = 38 | issue = 4 | pages = 363–71 | date = November 2005 | pmid = 16515737 | pmc = 3478329 | doi = 10.1017/S0033583505004087 }}</ref> Branched DNA can be used in [[nanotechnology]] to construct geometric shapes, see the section on [[#Uses in technology|uses in technology]] below.
=== Artificial bases ===
{{Main|Nucleic acid analogue}}
Several artificial nucleobases have been synthesized, and successfully incorporated in the eight-base DNA analogue named [[Hachimoji DNA]]. Dubbed S, B, P, and Z, these artificial bases are capable of bonding with each other in a predictable way (S–B and P–Z), maintain the double helix structure of DNA, and be transcribed to RNA. Their existence could be seen as an indication that there is nothing special about the four natural nucleobases that evolved on Earth.<ref>{{cite journal | vauthors = Warren M |title=Four new DNA letters double life's alphabet | journal = Nature |date=21 February 2019 | doi = 10.1038/d41586-019-00650-8 | pmid = 30809059 | volume=566 | issue = 7745 | page=436| doi-access = free | bibcode = 2019Natur.566..436W }}</ref><ref>{{cite journal| vauthors = Hoshika S, Leal NA, Kim MJ, Kim MS, Karalkar NB, Kim HJ, Bates AM, Watkins NE, SantaLucia HA, Meyer AJ, DasGupta S, Piccirilli JA, Ellington AD, SantaLucia J, Georgiadis MM, Benner SA | display-authors = 6 |title=Hachimoji DNA and RNA: A genetic system with eight building blocks (paywall)|journal=[[Science (journal)|Science]] |volume=363 |issue=6429 |pages=884–887 |date=22 February 2019 | doi = 10.1126/science.aat0971 | pmid = 30792304 | pmc=6413494 | bibcode=2019Sci...363..884H}}</ref> On the other hand, DNA is tightly related to [[RNA]] which does not only act as a transcript of DNA but also performs as molecular machines many tasks in cells. For this purpose it has to fold into a structure. It has been shown that to allow to create all possible structures at least four bases are required for the corresponding [[RNA]],<ref>{{cite journal | vauthors = Burghardt B, Hartmann AK | title = RNA secondary structure design | journal = Physical Review E | volume = 75 | issue = 2 | pages = 021920 | date = February 2007 | doi = 10.1103/PhysRevE.75.021920 | pmid = 17358380 | url = https://link.aps.org/doi/10.1103/PhysRevE.75.021920| arxiv = physics/0609135 | bibcode = 2007PhRvE..75b1920B | s2cid = 17574854 }}</ref> while a higher number is also possible but this would be against the natural [[principle of least effort]].
===Acidity===
The phosphate groups of DNA give it similar [[acid]]ic properties to [[phosphoric acid]] and it can be considered as a [[Acid strength|strong acid]]. It will be fully ionized at a normal cellular pH, releasing [[proton]]s which leave behind negative charges on the phosphate groups. These negative charges protect DNA from breakdown by [[hydrolysis]] by repelling [[nucleophile]]s which could hydrolyze it.<ref name="Reusch">{{cite web | vauthors = Reusch W |title=Nucleic Acids |url=https://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/nucacids.htm |publisher=Michigan State University |access-date=30 June 2022}}</ref>
===Macroscopic appearance===
[[File:Estrazione DNA (cropped).jpg|thumb|Impure DNA extracted from an orange]]
Pure DNA extracted from cells forms white, stringy clumps.<ref>{{cite web |title=How To Extract DNA From Anything Living |url=https://learn.genetics.utah.edu/content/labs/extraction/howto/ |publisher=University of Utah |access-date=30 June 2022}}</ref>
== Chemical modifications and altered DNA packaging ==
=== Base modifications and DNA packaging ===
{{further|DNA methylation|Chromatin remodeling}}
<div class="thumb tright" style="background:#f9f9f9; border:1px solid #ccc; margin:0.5em;">
{| border="0" cellpadding="2" cellspacing="0" style="width:300px; font-size:85%; border:1px solid #ccc; margin:0.3em;"
|-
|[[File:Cytosin.svg|75px]]
|[[File:5-Methylcytosine.svg|95px]]
|[[File:Thymin.svg|97px]]
|-
|align=center|[[cytosine]]
|align=center|[[5-Methylcytosine|5-methylcytosine]]
|align=center|[[thymine]]
|}
<div style="border: none; width:300px;font-size: 90%;"><div class="thumbcaption">Structure of cytosine with and without the 5-methyl group. [[Deamination]] converts 5-methylcytosine into thymine.</div></div></div>
The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called [[chromatin]]. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of [[methylation]] of [[cytosine]] bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the [[histone]] protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see [[Chromatin remodeling]]). There is, further, [[Crosstalk (biology)|crosstalk]] between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression.<ref>{{cite journal | vauthors = Hu Q, Rosenfeld MG | title = Epigenetic regulation of human embryonic stem cells | journal = Frontiers in Genetics | volume = 3 | pages = 238 | year = 2012 | pmid = 23133442 | pmc = 3488762 | doi = 10.3389/fgene.2012.00238 | doi-access = free }}</ref>
For one example, cytosine methylation produces [[5-Methylcytosine|5-methylcytosine]], which is important for [[X-inactivation]] of chromosomes.<ref>{{cite journal | vauthors = Klose RJ, Bird AP | title = Genomic DNA methylation: the mark and its mediators | journal = Trends in Biochemical Sciences | volume = 31 | issue = 2 | pages = 89–97 | date = February 2006 | pmid = 16403636 | doi = 10.1016/j.tibs.2005.12.008 }}</ref> The average level of methylation varies between organisms—the worm ''[[Caenorhabditis elegans]]'' lacks cytosine methylation, while [[vertebrate]]s have higher levels, with up to 1% of their DNA containing 5-methylcytosine.<ref>{{cite journal | vauthors = Bird A | title = DNA methylation patterns and epigenetic memory | journal = Genes & Development | volume = 16 | issue = 1 | pages = 6–21 | date = January 2002 | pmid = 11782440 | doi = 10.1101/gad.947102 | doi-access = free }}</ref> Despite the importance of 5-methylcytosine, it can [[deamination|deaminate]] to leave a thymine base, so methylated cytosines are particularly prone to [[mutation]]s.<ref>{{cite book | vauthors = Walsh CP, Xu GL | title = DNA Methylation: Basic Mechanisms | chapter = Cytosine methylation and DNA repair | volume = 301 | pages = 283–315 | year = 2006 | pmid = 16570853 | doi = 10.1007/3-540-31390-7_11 | isbn = 3-540-29114-8 | series = Current Topics in Microbiology and Immunology }}</ref> Other base modifications include adenine methylation in bacteria, the presence of [[5-hydroxymethylcytosine]] in the [[brain]],<ref>{{cite journal | vauthors = Kriaucionis S, Heintz N | title = The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain | journal = Science | volume = 324 | issue = 5929 | pages = 929–30 | date = May 2009 | pmid = 19372393 | pmc = 3263819 | doi = 10.1126/science.1169786 | bibcode = 2009Sci...324..929K }}</ref> and the [[glycosylation]] of uracil to produce the "J-base" in [[Kinetoplastida|kinetoplastids]].<ref>{{cite journal | vauthors = Ratel D, Ravanat JL, Berger F, Wion D | title = N6-methyladenine: the other methylated base of DNA | journal = BioEssays | volume = 28 | issue = 3 | pages = 309–15 | date = March 2006 | pmid = 16479578 | pmc = 2754416 | doi = 10.1002/bies.20342 }}</ref><ref>{{cite journal | vauthors = Gommers-Ampt JH, Van Leeuwen F, de Beer AL, Vliegenthart JF, Dizdaroglu M, Kowalak JA, Crain PF, Borst P | s2cid = 24801094 | title = beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei | journal = Cell | volume = 75 | issue = 6 | pages = 1129–36 | date = December 1993 | pmid = 8261512 | doi = 10.1016/0092-8674(93)90322-H | hdl = 1874/5219 | hdl-access = free }}</ref>
=== Damage ===
{{further|DNA damage (naturally occurring)|Mutation|DNA damage theory of aging}}
[[File:Benzopyrene DNA adduct 1JDG.png|thumb|right|A [[covalent]] [[adduct]] between a [[Cytochrome P450, family 1, member A1|metabolically activated]] form of [[Benzo(a)pyrene|benzo[''a'']pyrene]], the major [[mutagen]] in [[tobacco smoking|tobacco smoke]], and DNA<ref>Created from [http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1JDG PDB 1JDG] {{Webarchive|url=https://web.archive.org/web/20080922150848/http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1JDG |date=22 September 2008 }}</ref>]]
DNA can be damaged by many sorts of [[mutagen]]s, which change the [[DNA sequencing|DNA sequence]]. Mutagens include [[oxidizing agent]]s, [[Alkylation|alkylating agents]] and also high-energy [[electromagnetic radiation]] such as [[ultraviolet]] light and [[X-ray]]s. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing [[thymine dimer]]s, which are cross-links between pyrimidine bases.<ref>{{cite journal | vauthors = Douki T, Reynaud-Angelin A, Cadet J, Sage E | title = Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation | journal = Biochemistry | volume = 42 | issue = 30 | pages = 9221–26 | date = August 2003 | pmid = 12885257 | doi = 10.1021/bi034593c }}</ref> On the other hand, oxidants such as [[Radical (chemistry)|free radicals]] or [[hydrogen peroxide]] produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks.<ref>{{cite journal | vauthors = Cadet J, Delatour T, Douki T, Gasparutto D, Pouget JP, Ravanat JL, Sauvaigo S | title = Hydroxyl radicals and DNA base damage | journal = Mutation Research | volume = 424 | issue = 1–2 | pages = 9–21 | date = March 1999 | pmid = 10064846 | doi = 10.1016/S0027-5107(99)00004-4 | bibcode = 1999MRFMM.424....9C }}</ref> A typical human cell contains about 150,000 bases that have suffered oxidative damage.<ref>{{cite journal | vauthors = Beckman KB, Ames BN | title = Oxidative decay of DNA | journal = The Journal of Biological Chemistry | volume = 272 | issue = 32 | pages = 19633–36 | date = August 1997 | pmid = 9289489 | doi = 10.1074/jbc.272.32.19633 | doi-access = free }}</ref> Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce [[point mutation]]s, [[Genetic insertion|insertions]], [[Deletion (genetics)|deletions]] from the DNA sequence, and [[chromosomal translocation]]s.<ref>{{cite journal | vauthors = Valerie K, Povirk LF | title = Regulation and mechanisms of mammalian double-strand break repair | journal = Oncogene | volume = 22 | issue = 37 | pages = 5792–812 | date = September 2003 | pmid = 12947387 | doi = 10.1038/sj.onc.1206679 | doi-access = free }}</ref> These mutations can cause [[cancer]]. Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer.<ref name=Weinberg>{{cite news | url = https://www.nytimes.com/2010/12/28/health/28cancer.html | title = Unearthing Prehistoric Tumors, and Debate | newspaper = [[The New York Times]] | date = 28 December 2010 | vauthors = Johnson G | quote = If we lived long enough, sooner or later we all would get cancer. | url-status=live | archive-url = https://web.archive.org/web/20170624233156/http://www.nytimes.com/2010/12/28/health/28cancer.html | archive-date = 24 June 2017 | df = dmy-all }}</ref><ref>{{cite book |vauthors= Alberts B, Johnson A, Lewis J |title= Molecular biology of the cell |publisher= Garland Science |location= New York |year= 2002 |edition= 4th |chapter= The Preventable Causes of Cancer |isbn= 0-8153-4072-9 |chapter-url= https://www.ncbi.nlm.nih.gov/books/NBK26897/ |quote= A certain irreducible background incidence of cancer is to be expected regardless of circumstances: mutations can never be absolutely avoided, because they are an inescapable consequence of fundamental limitations on the accuracy of DNA replication, as discussed in Chapter 5. If a human could live long enough, it is inevitable that at least one of his or her cells would eventually accumulate a set of mutations sufficient for cancer to develop. |display-authors= etal |url-status=live |archive-url= https://web.archive.org/web/20160102193148/http://www.ncbi.nlm.nih.gov/books/NBK26897/ |archive-date= 2 January 2016 |df= dmy-all }}</ref> DNA damages that are [[DNA damage (naturally occurring)|naturally occurring]], due to normal cellular processes that produce reactive oxygen species, the hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging.<ref>{{cite book | veditors = Kimura H, Suzuki A | title = New Research on DNA Damage | date = 2008 | publisher = Nova Science Publishers | location = New York | isbn = 978-1-60456-581-2 | vauthors = Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K | chapter = Cancer and aging as consequences of un-repaired DNA damage | chapter-url = https://www.novapublishers.com/catalog/product_info.php?products_id=43247 | pages = 1–47 | url-status=live | archive-url = https://web.archive.org/web/20141025091740/https://www.novapublishers.com/catalog/product_info.php?products_id=43247 | archive-date = 25 October 2014 | df = dmy-all }}</ref><ref>{{cite journal | vauthors = Hoeijmakers JH | title = DNA damage, aging, and cancer | journal = The New England Journal of Medicine | volume = 361 | issue = 15 | pages = 1475–85 | date = October 2009 | pmid = 19812404 | doi = 10.1056/NEJMra0804615 }}</ref><ref>{{cite journal | vauthors = Freitas AA, de Magalhães JP | title = A review and appraisal of the DNA damage theory of ageing | journal = Mutation Research | volume = 728 | issue = 1–2 | pages = 12–22 | year = 2011 | pmid = 21600302 | doi = 10.1016/j.mrrev.2011.05.001 | bibcode = 2011MRRMR.728...12F }}</ref>
Many mutagens fit into the space between two adjacent base pairs, this is called ''[[intercalation (biochemistry)|intercalation]]''. Most intercalators are [[aromaticity|aromatic]] and planar molecules; examples include [[ethidium bromide]], [[acridine]]s, [[Daunorubicin|daunomycin]], and [[doxorubicin]]. For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations.<ref>{{cite journal | vauthors = Ferguson LR, Denny WA | title = The genetic toxicology of acridines | journal = Mutation Research | volume = 258 | issue = 2 | pages = 123–60 | date = September 1991 | pmid = 1881402 | doi = 10.1016/0165-1110(91)90006-H }}</ref> As a result, DNA intercalators may be [[carcinogen]]s, and in the case of thalidomide, a [[teratogen]].<ref>{{cite journal | vauthors = Stephens TD, Bunde CJ, Fillmore BJ | title = Mechanism of action in thalidomide teratogenesis | journal = Biochemical Pharmacology | volume = 59 | issue = 12 | pages = 1489–99 | date = June 2000 | pmid = 10799645 | doi = 10.1016/S0006-2952(99)00388-3 }}</ref> Others such as [[benzo(a)pyrene|benzo[''a'']pyrene diol epoxide]] and [[aflatoxin]] form DNA adducts that induce errors in replication.<ref>{{cite journal | vauthors = Jeffrey AM | title = DNA modification by chemical carcinogens | journal = Pharmacology & Therapeutics | volume = 28 | issue = 2 | pages = 237–72 | year = 1985 | pmid = 3936066 | doi = 10.1016/0163-7258(85)90013-0 }}</ref> Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in [[chemotherapy]] to inhibit rapidly growing [[cancer]] cells.<ref>{{cite journal | vauthors = Braña MF, Cacho M, Gradillas A, de Pascual-Teresa B, Ramos A | title = Intercalators as anticancer drugs | journal = Current Pharmaceutical Design | volume = 7 | issue = 17 | pages = 1745–80 | date = November 2001 | pmid = 11562309 | doi = 10.2174/1381612013397113 }}</ref>
== Biological functions ==
[[File:Eukaryote DNA-en.svg|thumb|upright=1.45|Location of eukaryote [[nuclear DNA]] within the chromosomes]]
DNA usually occurs as linear [[chromosome]]s in [[eukaryote]]s, and [[circular prokaryote chromosome|circular chromosomes]] in [[prokaryote]]s. The set of chromosomes in a cell makes up its [[genome]]; the [[human genome]] has approximately 3 billion base pairs of DNA arranged into 46 chromosomes.<ref name="Venter_2001" /> The information carried by DNA is held in the [[DNA sequence|sequence]] of pieces of DNA called [[gene]]s. [[Transmission (genetics)|Transmission]] of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching [[Peptide sequence|protein sequence]] in a process called [[Translation (biology)|translation]], which depends on the same interaction between RNA nucleotides. In an alternative fashion, a cell may copy its genetic information in a process called [[DNA replication]]. The details of these functions are covered in other articles; here the focus is on the interactions between DNA and other molecules that mediate the function of the genome.
=== Genes and genomes ===
{{further|Cell nucleus|Chromatin|Chromosome|Gene|Noncoding DNA}}
Genomic DNA is tightly and orderly packed in the process called [[DNA condensation]], to fit the small available volumes of the cell. In eukaryotes, DNA is located in the [[cell nucleus]], with small amounts in [[mitochondrion|mitochondria]] and [[chloroplast]]s. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the [[nucleoid]].<ref>{{cite journal | vauthors = Thanbichler M, Wang SC, Shapiro L | title = The bacterial nucleoid: a highly organized and dynamic structure | journal = Journal of Cellular Biochemistry | volume = 96 | issue = 3 | pages = 506–21 | date = October 2005 | pmid = 15988757 | doi = 10.1002/jcb.20519 | doi-access = free }}</ref> The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its [[genotype]]. A gene is a unit of [[heredity]] and is a region of DNA that influences a particular characteristic in an organism. Genes contain an [[open reading frame]] that can be transcribed, and [[regulatory sequence]]s such as [[promoter (biology)|promoters]] and [[enhancer (genetics)|enhancers]], which control transcription of the open reading frame.
In many [[species]], only a small fraction of the total sequence of the [[genome]] encodes protein. For example, only about 1.5% of the human genome consists of protein-coding [[exon]]s, with over 50% of human DNA consisting of non-coding [[repeated sequence (DNA)|repetitive sequences]].<ref>{{cite journal | vauthors = Wolfsberg TG, McEntyre J, Schuler GD | title = Guide to the draft human genome | journal = Nature | volume = 409 | issue = 6822 | pages = 824–26 | date = February 2001 | pmid = 11236998 | doi = 10.1038/35057000 | bibcode = 2001Natur.409..824W | url = https://zenodo.org/record/1233093 | doi-access = free }}</ref> The reasons for the presence of so much [[noncoding DNA]] in eukaryotic genomes and the extraordinary differences in [[genome size]], or ''[[C-value]]'', among species, represent a long-standing puzzle known as the "[[C-value enigma]]".<ref>{{cite journal | vauthors = Gregory TR | title = The C-value enigma in plants and animals: a review of parallels and an appeal for partnership | journal = Annals of Botany | volume = 95 | issue = 1 | pages = 133–46 | date = January 2005 | pmid = 15596463 | doi = 10.1093/aob/mci009 | pmc = 4246714 }}</ref> However, some DNA sequences that do not code protein may still encode functional [[non-coding RNA]] molecules, which are involved in the [[regulation of gene expression]].<ref name="Birney_2007" />
[[File:T7 RNA polymerase.jpg|thumb|[[T7 RNA polymerase]] (blue) producing an [[Messenger RNA|mRNA]] (green) from a DNA template (orange)<ref>{{Cite web| vauthors = Yin YW, Steitz TA |title=RCSB PDB – 1MSW: Structural basis for the transition from initiation to elongation transcription in T7 RNA polymerase|url=https://www.rcsb.org/structure/1MSW|access-date=2023-03-27|website=www.rcsb.org|language=en-US}}</ref>]]
Some noncoding DNA sequences play structural roles in chromosomes. [[Telomere]]s and [[centromere]]s typically contain few genes but are important for the function and stability of chromosomes.<ref name=Nugent /><ref>{{cite journal | vauthors = Pidoux AL, Allshire RC | title = The role of heterochromatin in centromere function | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 360 | issue = 1455 | pages = 569–79 | date = March 2005 | pmid = 15905142 | pmc = 1569473 | doi = 10.1098/rstb.2004.1611 }}</ref> An abundant form of noncoding DNA in humans are [[pseudogene]]s, which are copies of genes that have been disabled by mutation.<ref>{{cite journal | vauthors = Harrison PM, Hegyi H, Balasubramanian S, Luscombe NM, Bertone P, Echols N, Johnson T, Gerstein M | title = Molecular fossils in the human genome: identification and analysis of the pseudogenes in chromosomes 21 and 22 | journal = Genome Research | volume = 12 | issue = 2 | pages = 272–80 | date = February 2002 | pmid = 11827946 | pmc = 155275 | doi = 10.1101/gr.207102 }}</ref> These sequences are usually just molecular [[fossil]]s, although they can occasionally serve as raw [[Genome|genetic material]] for the creation of new genes through the process of [[gene duplication]] and [[divergent evolution|divergence]].<ref>{{cite journal | vauthors = Harrison PM, Gerstein M | title = Studying genomes through the aeons: protein families, pseudogenes and proteome evolution | journal = Journal of Molecular Biology | volume = 318 | issue = 5 | pages = 1155–74 | date = May 2002 | pmid = 12083509 | doi = 10.1016/S0022-2836(02)00109-2 }}</ref>
=== Transcription and translation ===
{{further|Genetic code|Transcription (genetics)|Protein biosynthesis}}
A gene is a sequence of DNA that contains genetic information and can influence the [[phenotype]] of an organism. Within a gene, the sequence of bases along a DNA strand defines a [[messenger RNA]] sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the [[amino acid|amino-acid]] sequences of proteins is determined by the rules of [[Translation (biology)|translation]], known collectively as the [[genetic code]]. The genetic code consists of three-letter 'words' called ''codons'' formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).
In transcription, the codons of a gene are copied into messenger RNA by [[RNA polymerase]]. This RNA copy is then decoded by a [[ribosome]] that reads the RNA sequence by base-pairing the messenger RNA to [[transfer RNA]], which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (4<sup>3</sup>&nbsp;combinations). These encode the twenty [[list of standard amino acids|standard amino acids]], giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAG, TAA, and TGA codons, (UAG, UAA, and UGA on the mRNA).
=== Replication ===
{{further|DNA replication}}
[[File:DNA replication en.svg|thumb|upright=1.78|right|DNA replication: The double helix is unwound by a [[helicase]] and [[topoisomerase|topo&shy;iso&shy;merase]]. Next, one [[DNA polymerase]] produces the [[Replication fork|leading strand]] copy. Another DNA polymerase binds to the [[Replication fork|lagging strand]]. This enzyme makes discontinuous segments (called [[Okazaki fragment]]s) before [[DNA ligase]] joins them together.]]
[[Cell division]] is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for [[DNA replication]]. Here, the two strands are separated and then each strand's [[complementary DNA]] sequence is recreated by an [[enzyme]] called [[DNA polymerase]]. This enzyme makes the complementary strand by finding the correct base through complementary base pairing and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5′ to 3′ direction, different mechanisms are used to copy the antiparallel strands of the double helix.<ref>{{cite journal | vauthors = Albà M | title = Replicative DNA polymerases | journal = Genome Biology | volume = 2 | issue = 1 | pages = REVIEWS3002 | year = 2001 | pmid = 11178285 | pmc = 150442 | doi = 10.1186/gb-2001-2-1-reviews3002 | doi-access = free }}</ref> In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.
=== Extracellular nucleic acids ===
Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 μg/L, and its concentration in natural aquatic environments may be as high at 88 μg/L.<ref name=Tani_2010>{{cite book | vauthors = Tani K, Nasu M | veditors = Kikuchi Y, Rykova EY | title = Extracellular Nucleic Acids |url=https://archive.org/details/extracellularnuc00kiku |url-access=limited |publisher=Springer |date=2010 |pages=[https://archive.org/details/extracellularnuc00kiku/page/n35 25]–38 |chapter=Roles of Extracellular DNA in Bacterial Ecosystems |isbn=978-3-642-12616-1}}</ref> Various possible functions have been proposed for eDNA: it may be involved in [[horizontal gene transfer]];<ref name="Vlassov_2007">{{cite journal | vauthors = Vlassov VV, Laktionov PP, Rykova EY | title = Extracellular nucleic acids | journal = BioEssays | volume = 29 | issue = 7 | pages = 654–67 | date = July 2007 | pmid = 17563084 | doi = 10.1002/bies.20604 | s2cid = 32463239 }}</ref> it may provide nutrients;<ref name="pmid11591672">{{cite journal | vauthors = Finkel SE, Kolter R | title = DNA as a nutrient: novel role for bacterial competence gene homologs | journal = Journal of Bacteriology | volume = 183 | issue = 21 | pages = 6288–93 | date = November 2001 | pmid = 11591672 | pmc = 100116 | doi = 10.1128/JB.183.21.6288-6293.2001 }}</ref> and it may act as a buffer to recruit or titrate ions or antibiotics.<ref name=Mulcahy_2008>{{cite journal | vauthors = Mulcahy H, Charron-Mazenod L, Lewenza S | title = Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms | journal = PLOS Pathogens | volume = 4 | issue = 11 | pages = e1000213 | date = November 2008 | pmid = 19023416 | pmc = 2581603 | doi = 10.1371/journal.ppat.1000213 | doi-access = free }}</ref> Extracellular DNA acts as a functional extracellular matrix component in the [[biofilm]]s of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm;<ref name=Berne_2010>{{cite journal | vauthors = Berne C, Kysela DT, Brun YV | title = A bacterial extracellular DNA inhibits settling of motile progeny cells within a biofilm | journal = Molecular Microbiology | volume = 77 | issue = 4 | pages = 815–29 | date = August 2010 | pmid = 20598083 | pmc = 2962764 | doi = 10.1111/j.1365-2958.2010.07267.x }}</ref> it may contribute to biofilm formation;<ref name=Whitchurch_2002>{{cite journal | vauthors = Whitchurch CB, Tolker-Nielsen T, Ragas PC, Mattick JS | title = Extracellular DNA required for bacterial biofilm formation | journal = Science | volume = 295 | issue = 5559 | pages = 1487 | date = February 2002 | pmid = 11859186 | doi = 10.1126/science.295.5559.1487 }}</ref> and it may contribute to the biofilm's physical strength and resistance to biological stress.<ref name=Hu_2012>{{cite journal | vauthors = Hu W, Li L, Sharma S, Wang J, McHardy I, Lux R, Yang Z, He X, Gimzewski JK, Li Y, Shi W | title = DNA builds and strengthens the extracellular matrix in Myxococcus xanthus biofilms by interacting with exopolysaccharides | journal = PLOS ONE | volume = 7 | issue = 12 | pages = e51905 | year = 2012 | pmid = 23300576 | pmc = 3530553 | doi = 10.1371/journal.pone.0051905 | bibcode = 2012PLoSO...751905H | doi-access = free }}</ref>
[[Cell-free fetal DNA]] is found in the blood of the mother, and can be sequenced to determine a great deal of information about the developing fetus.<ref name="Hui_2013">{{cite journal | vauthors = Hui L, Bianchi DW | title = Recent advances in the prenatal interrogation of the human fetal genome | journal = Trends in Genetics | volume = 29 | issue = 2 | pages = 84–91 | date = February 2013 | pmid = 23158400 | pmc = 4378900 | doi = 10.1016/j.tig.2012.10.013 }}</ref>
Under the name of [[environmental DNA]] eDNA has seen increased use in the natural sciences as a survey tool for [[ecology]], monitoring the movements and presence of species in water, air, or on land, and assessing an area's biodiversity.<ref>{{cite journal | vauthors = Foote AD, Thomsen PF, Sveegaard S, Wahlberg M, Kielgast J, Kyhn LA, Salling AB, Galatius A, Orlando L, Gilbert MT | display-authors = 6 | title = Investigating the potential use of environmental DNA (eDNA) for genetic monitoring of marine mammals | journal = PLOS ONE | volume = 7 | issue = 8 | pages = e41781 | year = 2012 | pmid = 22952587 | pmc = 3430683 | doi = 10.1371/journal.pone.0041781 | bibcode = 2012PLoSO...741781F | doi-access = free }}</ref><ref>{{Cite web | url=https://www.the-scientist.com/news-opinion/researchers-detect-land-animals-using-dna-in-nearby-water-bodies-67481 | title=Researchers Detect Land Animals Using DNA in Nearby Water Bodies}}</ref>
=== Neutrophil extracellular traps ===
{{Main|Neutrophil extracellular traps}}
Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA, which allow [[neutrophils]], a type of white blood cell, to kill extracellular pathogens while minimizing damage to the host cells.
== Interactions with proteins ==
All the functions of DNA depend on interactions with proteins. These [[protein interactions]] can be non-specific, or the protein can bind specifically to a single DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.
=== DNA-binding proteins ===
{{further|DNA-binding protein}}
[[File:Nucleosome1.png|thumb|260px|left|Interaction of DNA (in orange) with [[histone]]s (in blue). These proteins' basic amino acids bind to the acidic phosphate groups on DNA.]]
Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called [[chromatin]]. In eukaryotes, this structure involves DNA binding to a complex of small basic proteins called [[histone]]s, while in prokaryotes multiple types of proteins are involved.<ref>{{cite journal | vauthors = Sandman K, Pereira SL, Reeve JN | s2cid = 21101836 | title = Diversity of prokaryotic chromosomal proteins and the origin of the nucleosome | journal = Cellular and Molecular Life Sciences | volume = 54 | issue = 12 | pages = 1350–64 | date = December 1998 | pmid = 9893710 | doi = 10.1007/s000180050259 | pmc = 11147202 }}</ref><ref>{{cite journal | vauthors = Dame RT | title = The role of nucleoid-associated proteins in the organization and compaction of bacterial chromatin | journal = Molecular Microbiology | volume = 56 | issue = 4 | pages = 858–70 | date = May 2005 | pmid = 15853876 | doi = 10.1111/j.1365-2958.2005.04598.x | s2cid = 26965112 | doi-access = free }}</ref> The histones form a disk-shaped complex called a [[nucleosome]], which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones, making [[ionic bond]]s to the acidic sugar-phosphate backbone of the DNA, and are thus largely independent of the base sequence.<ref>{{cite journal | vauthors = Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ | title = Crystal structure of the nucleosome core particle at 2.8 A resolution | journal = Nature | volume = 389 | issue = 6648 | pages = 251–60 | date = September 1997 | pmid = 9305837 | doi = 10.1038/38444 | bibcode = 1997Natur.389..251L | s2cid = 4328827 }}</ref> Chemical modifications of these basic amino acid residues include [[methylation]], [[phosphorylation]], and [[acetylation]].<ref>{{cite journal | vauthors = Jenuwein T, Allis CD | title = Translating the histone code | journal = Science | volume = 293 | issue = 5532 | pages = 1074–80 | date = August 2001 | pmid = 11498575 | doi = 10.1126/science.1063127 | s2cid = 1883924 | url = http://www.gs.washington.edu/academics/courses/braun/55104/readings/jenuwein.pdf | url-status=live | archive-url = https://web.archive.org/web/20170808142426/http://www.gs.washington.edu/academics/courses/braun/55104/readings/jenuwein.pdf | archive-date = 8 August 2017 | df = dmy-all }}</ref> These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to [[transcription factor]]s and changing the rate of transcription.<ref>{{cite book | vauthors = Ito T | title = Protein Complexes that Modify Chromatin | chapter = Nucleosome Assembly and Remodeling | series = Current Topics in Microbiology and Immunology | volume = 274 | pages = 1–22 | year = 2003 | pmid = 12596902 | doi = 10.1007/978-3-642-55747-7_1 | isbn = 978-3-540-44208-0 }}</ref> Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA.<ref>{{cite journal | vauthors = Thomas JO | title = HMG1 and 2: architectural DNA-binding proteins | journal = Biochemical Society Transactions | volume = 29 | issue = Pt 4 | pages = 395–401 | date = August 2001 | pmid = 11497996 | doi = 10.1042/BST0290395 }}</ref> These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.<ref>{{cite journal | vauthors = Grosschedl R, Giese K, Pagel J | title = HMG domain proteins: architectural elements in the assembly of nucleoprotein structures | journal = Trends in Genetics | volume = 10 | issue = 3 | pages = 94–100 | date = March 1994 | pmid = 8178371 | doi = 10.1016/0168-9525(94)90232-1 }}</ref>
A distinct group of DNA-binding proteins is the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication [[protein A]] is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination, and DNA repair.<ref>{{cite journal | vauthors = Iftode C, Daniely Y, Borowiec JA | title = Replication protein A (RPA): the eukaryotic SSB | journal = Critical Reviews in Biochemistry and Molecular Biology | volume = 34 | issue = 3 | pages = 141–80 | year = 1999 | pmid = 10473346 | doi = 10.1080/10409239991209255 }}</ref> These binding proteins seem to stabilize single-stranded DNA and protect it from forming [[stem-loop]]s or being degraded by [[nuclease]]s.
[[File:Lambda repressor 1LMB.png|thumb|upright=1.1|The lambda repressor [[helix-turn-helix]] transcription factor bound to its DNA target<ref>{{Cite web| vauthors = Beamer LJ, Pabo CO |title=RCSB PDB – 1LMB: Refined 1.8 Å crystal structure of the lambda repressor-operator complex |url=https://www.rcsb.org/structure/1LMB|access-date=2023-03-27|website=www.rcsb.org|language=en-US}}</ref>]]
In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various [[transcription factor]]s, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription.<ref>{{cite journal | vauthors = Myers LC, Kornberg RD | title = Mediator of transcriptional regulation | journal = Annual Review of Biochemistry | volume = 69 | pages = 729–49 | year = 2000 | pmid = 10966474 | doi = 10.1146/annurev.biochem.69.1.729 }}</ref> Alternatively, transcription factors can bind [[enzyme]]s that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase.<ref>{{cite journal | vauthors = Spiegelman BM, Heinrich R | title = Biological control through regulated transcriptional coactivators | journal = Cell | volume = 119 | issue = 2 | pages = 157–67 | date = October 2004 | pmid = 15479634 | doi = 10.1016/j.cell.2004.09.037 | doi-access = free }}</ref>
As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes.<ref>{{cite journal | vauthors = Li Z, Van Calcar S, Qu C, Cavenee WK, Zhang MQ, Ren B | title = A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 14 | pages = 8164–69 | date = July 2003 | pmid = 12808131 | pmc = 166200 | doi = 10.1073/pnas.1332764100 | bibcode = 2003PNAS..100.8164L | doi-access = free }}</ref> Consequently, these proteins are often the targets of the [[signal transduction]] processes that control responses to environmental changes or [[cellular differentiation]] and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.<ref name="Pabo1984" />
=== DNA-modifying enzymes ===
==== Nucleases and ligases ====
[[File:EcoRV 1RVA.png|thumb|left|upright=1.1|The [[restriction enzyme]] [[EcoRV]] (green) in a complex with its substrate DNA<ref>{{Cite web| vauthors = Kostrewa D, Winkler FK |title=RCSB PDB – 1RVA: Mg2+ binding to the active site of EcoRV endonuclease: a crystallographic study of complexes with substrate and product DNA at 2 Å resolution |url=https://www.rcsb.org/structure/1RVA|access-date=2023-03-27|website=www.rcsb.org|language=en-US}}</ref>]]
[[Nuclease]]s are [[enzyme]]s that cut DNA strands by catalyzing the [[hydrolysis]] of the [[phosphodiester bond]]s. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called [[exonuclease]]s, while [[endonuclease]]s cut within strands. The most frequently used nucleases in [[molecular biology]] are the [[restriction enzyme|restriction endonucleases]], which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5′-GATATC-3′ and makes a cut at the horizontal line. In nature, these enzymes protect [[bacteria]] against [[Bacteriophage|phage]] infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the [[restriction modification system]].<ref>{{cite journal | vauthors = Bickle TA, Krüger DH | title = Biology of DNA restriction | journal = Microbiological Reviews | volume = 57 | issue = 2 | pages = 434–50 | date = June 1993 | pmid = 8336674 | pmc = 372918 | doi = 10.1128/MMBR.57.2.434-450.1993 }}</ref> In technology, these sequence-specific nucleases are used in [[molecular cloning]] and [[Genetic fingerprinting|DNA fingerprinting]].
Enzymes called [[DNA ligase]]s can rejoin cut or broken DNA strands.<ref name=Doherty>{{cite journal | vauthors = Doherty AJ, Suh SW | title = Structural and mechanistic conservation in DNA ligases | journal = Nucleic Acids Research | volume = 28 | issue = 21 | pages = 4051–58 | date = November 2000 | pmid = 11058099 | pmc = 113121 | doi = 10.1093/nar/28.21.4051 }}</ref> Ligases are particularly important in [[Replication fork|lagging strand]] DNA replication, as they join the short segments of DNA produced at the [[replication fork]] into a complete copy of the DNA template. They are also used in [[DNA repair]] and [[genetic recombination]].<ref name=Doherty />
==== Topoisomerases and helicases ====
[[Topoisomerase]]s are enzymes with both nuclease and ligase activity. These proteins change the amount of [[DNA supercoil|supercoiling]] in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break.<ref name=Champoux /> Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix.<ref>{{cite journal | vauthors = Schoeffler AJ, Berger JM | title = Recent advances in understanding structure-function relationships in the type II topoisomerase mechanism | journal = Biochemical Society Transactions | volume = 33 | issue = Pt 6 | pages = 1465–70 | date = December 2005 | pmid = 16246147 | doi = 10.1042/BST20051465 }}</ref> Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.<ref name=Wang />
[[Helicase]]s are proteins that are a type of [[molecular motor]]. They use the chemical energy in [[nucleoside triphosphate]]s, predominantly [[adenosine triphosphate]] (ATP), to break hydrogen bonds between bases and unwind the DNA double helix into single strands.<ref>{{cite journal | vauthors = Tuteja N, Tuteja R | title = Unraveling DNA helicases. Motif, structure, mechanism and function | journal = European Journal of Biochemistry | volume = 271 | issue = 10 | pages = 1849–63 | date = May 2004 | pmid = 15128295 | doi = 10.1111/j.1432-1033.2004.04094.x | url = http://repository.ias.ac.in/52775/1/40-pub.pdf | doi-access = free }}</ref> These enzymes are essential for most processes where enzymes need to access the DNA bases.
==== Polymerases ====
[[Polymerase]]s are [[enzyme]]s that synthesize polynucleotide chains from [[nucleoside triphosphate]]s. The sequence of their products is created based on existing polynucleotide chains—which are called ''templates''. These enzymes function by repeatedly adding a nucleotide to the 3′ [[hydroxyl]] group at the end of the growing polynucleotide chain. As a consequence, all polymerases work in a 5′ to 3′ direction.<ref name=Joyce>{{cite journal | vauthors = Joyce CM, Steitz TA | title = Polymerase structures and function: variations on a theme? | journal = Journal of Bacteriology | volume = 177 | issue = 22 | pages = 6321–29 | date = November 1995 | pmid = 7592405 | pmc = 177480 | doi=10.1128/jb.177.22.6321-6329.1995}}</ref> In the [[active site]] of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use.
In DNA replication, DNA-dependent [[DNA polymerase]]s make copies of DNA polynucleotide chains. To preserve biological information, it is essential that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a [[Proofreading (biology)|proofreading]] activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3′ to 5′ [[exonuclease]] activity is activated and the incorrect base removed.<ref>{{cite journal | vauthors = Hubscher U, Maga G, Spadari S | s2cid = 26171993 | title = Eukaryotic DNA polymerases | journal = Annual Review of Biochemistry | volume = 71 | pages = 133–63 | year = 2002 | pmid = 12045093 | doi = 10.1146/annurev.biochem.71.090501.150041 | url = http://pdfs.semanticscholar.org/e941/98efed7eb8fa606b87d9a44c118c235a62e9.pdf | archive-url = https://web.archive.org/web/20210126170051/http://pdfs.semanticscholar.org/e941/98efed7eb8fa606b87d9a44c118c235a62e9.pdf | url-status = dead | archive-date = 26 January 2021 }}</ref> In most organisms, DNA polymerases function in a large complex called the [[replisome]] that contains multiple accessory subunits, such as the [[DNA clamp]] or [[helicase]]s.<ref>{{cite journal | vauthors = Johnson A, O'Donnell M | title = Cellular DNA replicases: components and dynamics at the replication fork | journal = Annual Review of Biochemistry | volume = 74 | pages = 283–315 | year = 2005 | pmid = 15952889 | doi = 10.1146/annurev.biochem.73.011303.073859 }}</ref>
RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include [[reverse transcriptase]], which is a [[virus|viral]] enzyme involved in the infection of cells by [[retrovirus]]es, and [[telomerase]], which is required for the replication of telomeres.<ref name=Greider /><ref name=Tarrago-Litvak1994>{{cite journal | vauthors = Tarrago-Litvak L, Andréola ML, Nevinsky GA, Sarih-Cottin L, Litvak S | title = The reverse transcriptase of HIV-1: from enzymology to therapeutic intervention | journal = FASEB Journal | volume = 8 | issue = 8 | pages = 497–503 | date = May 1994 | pmid = 7514143 | doi = 10.1096/fasebj.8.8.7514143 | doi-access = free | s2cid = 39614573 }}</ref> For example, HIV reverse transcriptase is an enzyme for AIDS virus replication.<ref name=Tarrago-Litvak1994 /> Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure. It synthesizes [[telomeres]] at the ends of chromosomes. Telomeres prevent fusion of the ends of neighboring chromosomes and protect chromosome ends from damage.<ref name=Nugent />
Transcription is carried out by a DNA-dependent [[RNA polymerase]] that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a [[messenger RNA]] transcript until it reaches a region of DNA called the [[terminator (genetics)|terminator]], where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, [[RNA polymerase II]], the enzyme that transcribes most of the genes in the human genome, operates as part of a large [[protein complex]] with multiple regulatory and accessory subunits.<ref>{{cite journal | vauthors = Martinez E | s2cid = 24946189 | title = Multi-protein complexes in eukaryotic gene transcription | journal = Plant Molecular Biology | volume = 50 | issue = 6 | pages = 925–47 | date = December 2002 | pmid = 12516863 | doi = 10.1023/A:1021258713850 }}</ref>
== Genetic recombination ==
{{further|Genetic recombination}}
<div class="thumb tright" style="background:#f9f9f9; border:1px solid #ccc; margin:0.5em;">
{| border="0" cellpadding="0" cellspacing="0" style="width:250px; font-size:85%; border:1px solid #ccc; margin:0.3em;"
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|[[File:Holliday Junction.svg|250px]]
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|[[File:Holliday junction coloured.png|250px]]
|}
<div style="border: none; width:250px;"><div class="thumbcaption">Structure of the [[Holliday junction]] intermediate in [[genetic recombination]]. The four separate DNA strands are coloured red, blue, green and yellow.<ref>{{Cite web| vauthors = Thorpe JH, Gale BC, Teixeira SC, Cardin CJ |title=RCSB PDB – 1M6G: Structural Characterisation of the Holliday Junction TCGGTACCGA|url=https://www.rcsb.org/structure/1M6G|access-date=2023-03-27|website=www.rcsb.org|language=en-US}}</ref></div></div></div>
[[File:Homologous Recombination.jpg|thumb|300px| A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.]]
A DNA helix usually does not interact with other segments of DNA, and in human cells, the different chromosomes even occupy separate areas in the nucleus called "[[chromosome territories]]".<ref>{{cite journal | vauthors = Cremer T, Cremer C | title = Chromosome territories, nuclear architecture and gene regulation in mammalian cells | journal = Nature Reviews Genetics | volume = 2 | issue = 4 | pages = 292–301 | date = April 2001 | pmid = 11283701 | doi = 10.1038/35066075 | s2cid = 8547149 }}</ref> This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is in [[chromosomal crossover]] which occurs during [[sexual reproduction]], when [[genetic recombination]] occurs. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.
Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of [[natural selection]] and can be important in the rapid evolution of new proteins.<ref>{{cite journal | vauthors = Pál C, Papp B, Lercher MJ | title = An integrated view of protein evolution | journal = Nature Reviews Genetics | volume = 7 | issue = 5 | pages = 337–48 | date = May 2006 | pmid = 16619049 | doi = 10.1038/nrg1838 | s2cid = 23225873 }}</ref> Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.<ref>{{cite journal | vauthors = O'Driscoll M, Jeggo PA | title = The role of double-strand break repair – insights from human genetics | journal = Nature Reviews Genetics | volume = 7 | issue = 1 | pages = 45–54 | date = January 2006 | pmid = 16369571 | doi = 10.1038/nrg1746 | s2cid = 7779574 }}</ref>
The most common form of chromosomal crossover is [[homologous recombination]], where the two chromosomes involved share very similar sequences. [[Non-homologous recombination]] can be damaging to cells, as it can produce [[chromosomal translocation]]s and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as [[recombinase]]s, such as [[RAD51]].<ref>{{cite journal | vauthors = Vispé S, Defais M | title = Mammalian Rad51 protein: a RecA homologue with pleiotropic functions | journal = Biochimie | volume = 79 | issue = 9–10 | pages = 587–92 | date = October 1997 | pmid = 9466696 | doi = 10.1016/S0300-9084(97)82007-X }}</ref> The first step in recombination is a double-stranded break caused by either an [[endonuclease]] or damage to the DNA.<ref>{{cite journal | vauthors = Neale MJ, Keeney S | title = Clarifying the mechanics of DNA strand exchange in meiotic recombination | journal = Nature | volume = 442 | issue = 7099 | pages = 153–58 | date = July 2006 | pmid = 16838012 | doi = 10.1038/nature04885 | bibcode = 2006Natur.442..153N | pmc = 5607947 }}</ref> A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one [[Holliday junction]], in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA.<ref>{{cite journal | vauthors = Dickman MJ, Ingleston SM, Sedelnikova SE, Rafferty JB, Lloyd RG, Grasby JA, Hornby DP | s2cid = 39505263 | title = The RuvABC resolvasome | journal = European Journal of Biochemistry | volume = 269 | issue = 22 | pages = 5492–501 | date = November 2002 | pmid = 12423347 | doi = 10.1046/j.1432-1033.2002.03250.x | doi-access = free }}</ref> Only strands of like polarity exchange DNA during recombination. There are two types of cleavage: east-west cleavage and north–south cleavage. The north–south cleavage nicks both strands of DNA, while the east–west cleavage has one strand of DNA intact. The formation of a Holliday junction during recombination makes it possible for genetic diversity, genes to exchange on chromosomes, and expression of wild-type viral genomes.
== Evolution ==
{{further|RNA world hypothesis}}
DNA contains the genetic information that allows all forms of life to function, grow and reproduce. However, it is unclear how long in the 4-billion-year [[Timeline of evolution|history of life]] DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material.<ref name="Joyce-2002">{{cite journal | vauthors = Joyce GF | title = The antiquity of RNA-based evolution | journal = Nature | volume = 418 | issue = 6894 | pages = 214–21 | date = July 2002 | pmid = 12110897 | doi = 10.1038/418214a | bibcode = 2002Natur.418..214J | s2cid = 4331004 }}</ref><ref>{{cite journal | vauthors = Orgel LE | title = Prebiotic chemistry and the origin of the RNA world | journal = Critical Reviews in Biochemistry and Molecular Biology | volume = 39 | issue = 2 | pages = 99–123 | year = 2004 | pmid = 15217990 | doi = 10.1080/10409230490460765 | citeseerx = 10.1.1.537.7679 | s2cid = 4939632 }}</ref> RNA may have acted as the central part of early [[cell metabolism]] as it can both transmit genetic information and carry out [[catalysis]] as part of [[ribozyme]]s.<ref>{{cite journal | vauthors = Davenport RJ | s2cid = 85976762 | title = Ribozymes. Making copies in the RNA world | journal = Science | volume = 292 | issue = 5520 | pages = 1278a–1278 | date = May 2001 | pmid = 11360970 | doi = 10.1126/science.292.5520.1278a }}</ref> This ancient [[RNA world hypothesis|RNA world]] where nucleic acid would have been used for both catalysis and genetics may have influenced the [[evolution]] of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication accuracy and a large number of bases increasing the catalytic efficiency of ribozymes.<ref>{{cite journal | vauthors = Szathmáry E | title = What is the optimum size for the genetic alphabet? | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 7 | pages = 2614–18 | date = April 1992 | pmid = 1372984 | pmc = 48712 | doi = 10.1073/pnas.89.7.2614 | bibcode = 1992PNAS...89.2614S | doi-access = free }}</ref> However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible because DNA survives in the environment for less than one million years, and slowly degrades into short fragments in solution.<ref>{{cite journal | vauthors = Lindahl T | title = Instability and decay of the primary structure of DNA | journal = Nature | volume = 362 | issue = 6422 | pages = 709–15 | date = April 1993 | pmid = 8469282 | doi = 10.1038/362709a0 | bibcode = 1993Natur.362..709L | s2cid = 4283694 }}</ref> Claims for older DNA have been made, most notably a report of the isolation of a viable bacterium from a salt crystal 250 million years old,<ref>{{cite journal | vauthors = Vreeland RH, Rosenzweig WD, Powers DW | title = Isolation of a 250 million-year-old halotolerant bacterium from a primary salt crystal | journal = Nature | volume = 407 | issue = 6806 | pages = 897–900 | date = October 2000 | pmid = 11057666 | doi = 10.1038/35038060 | bibcode = 2000Natur.407..897V | s2cid = 9879073 }}</ref> but these claims are controversial.<ref>{{cite journal | vauthors = Hebsgaard MB, Phillips MJ, Willerslev E | title = Geologically ancient DNA: fact or artefact? | journal = Trends in Microbiology | volume = 13 | issue = 5 | pages = 212–20 | date = May 2005 | pmid = 15866038 | doi = 10.1016/j.tim.2005.03.010 }}</ref><ref>{{cite journal | vauthors = Nickle DC, Learn GH, Rain MW, Mullins JI, Mittler JE | title = Curiously modern DNA for a "250 million-year-old" bacterium | journal = Journal of Molecular Evolution | volume = 54 | issue = 1 | pages = 134–37 | date = January 2002 | pmid = 11734907 | doi = 10.1007/s00239-001-0025-x | bibcode = 2002JMolE..54..134N | s2cid = 24740859 }}</ref>
Building blocks of DNA ([[adenine]], [[guanine]], and related [[organic molecules]]) may have been formed extraterrestrially in [[outer space]].<ref name="Callahan">{{cite journal | vauthors = Callahan MP, Smith KE, Cleaves HJ, Ruzicka J, Stern JC, Glavin DP, House CH, Dworkin JP | title = Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 34 | pages = 13995–98 | date = August 2011 | pmid = 21836052 | pmc = 3161613 | doi = 10.1073/pnas.1106493108 | bibcode = 2011PNAS..10813995C | doi-access = free }}</ref><ref name="Steigerwald">{{cite web | vauthors = Steigerwald J |title=NASA Researchers: DNA Building Blocks Can Be Made in Space |url=http://www.nasa.gov/topics/solarsystem/features/dna-meteorites.html |publisher=[[NASA]] |date=8 August 2011 |access-date=10 August 2011 |url-status=live |archive-url=https://web.archive.org/web/20150623004556/http://www.nasa.gov/topics/solarsystem/features/dna-meteorites.html |archive-date=23 June 2015 }}</ref><ref name="DNA">{{cite web |author=ScienceDaily Staff |title=DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests |url=https://www.sciencedaily.com/releases/2011/08/110808220659.htm |date=9 August 2011 |website=[[ScienceDaily]] |access-date=9 August 2011 |url-status=live |archive-url=https://web.archive.org/web/20110905105043/https://www.sciencedaily.com/releases/2011/08/110808220659.htm |archive-date=5 September 2011 }}</ref> Complex DNA and [[RNA]] [[organic compound]]s of [[life]], including [[uracil]], [[cytosine]], and [[thymine]], have also been formed in the laboratory under conditions mimicking those found in [[outer space]], using starting chemicals, such as [[pyrimidine]], found in [[meteorite]]s. Pyrimidine, like [[polycyclic aromatic hydrocarbons]] (PAHs), the most carbon-rich chemical found in the [[universe]], may have been formed in [[red giant]]s or in interstellar [[cosmic dust]] and gas clouds.<ref name="NASA-20150303">{{cite web | vauthors = Marlaire R |title=NASA Ames Reproduces the Building Blocks of Life in Laboratory |url=http://www.nasa.gov/content/nasa-ames-reproduces-the-building-blocks-of-life-in-laboratory |date=3 March 2015 |work=[[NASA]] |access-date=5 March 2015 |url-status=live |archive-url=https://web.archive.org/web/20150305083306/http://www.nasa.gov/content/nasa-ames-reproduces-the-building-blocks-of-life-in-laboratory/ |archive-date=5 March 2015 }}</ref>
[[Ancient DNA]] has been recovered from ancient organisms at a timescale where genome evolution can be directly observed, including from extinct organisms up to millions of years old, such as the [[woolly mammoth]].<ref name="CNN-20210217">{{cite news | vauthors = Hunt K |title=World's oldest DNA sequenced from a mammoth that lived more than a million years ago |url=https://www.cnn.com/2021/02/17/world/mammoth-oldest-dna-million-years-ago-scn/index.html |date=17 February 2021 |work=[[CNN|CNN News]] |access-date=17 February 2021 }}</ref><ref name="NAT-20210217">{{cite journal | vauthors = Callaway E | title = Million-year-old mammoth genomes shatter record for oldest ancient DNA – Permafrost-preserved teeth, up to 1.6 million years old, identify a new kind of mammoth in Siberia. |date=17 February 2021 |journal=[[Nature (journal)|Nature]] |volume=590 |issue=7847 |pages=537–538 |doi=10.1038/d41586-021-00436-x |issn=0028-0836 |pmid=33597786 | bibcode = 2021Natur.590..537C |doi-access=free }}</ref>
== Uses in technology ==
=== Genetic engineering ===
{{further|Molecular biology|Nucleic acid methods|Genetic engineering}}
Methods have been developed to purify DNA from organisms, such as [[phenol-chloroform extraction]], and to manipulate it in the laboratory, such as [[restriction digest]]s and the [[polymerase chain reaction]]. Modern [[biology]] and [[biochemistry]] make intensive use of these techniques in recombinant DNA technology. [[Recombinant DNA]] is a man-made DNA sequence that has been assembled from other DNA sequences. They can be [[transformation (genetics)|transformed]] into organisms in the form of [[plasmid]]s or in the appropriate format, by using a [[viral vector]].<ref>{{cite journal | vauthors = Goff SP, Berg P | s2cid = 41788896 | title = Construction of hybrid viruses containing SV40 and lambda phage DNA segments and their propagation in cultured monkey cells | journal = Cell | volume = 9 | issue = 4 PT 2 | pages = 695–705 | date = December 1976 | pmid = 189942 | doi = 10.1016/0092-8674(76)90133-1 }}</ref> The [[genetic engineering|genetically modified]] organisms produced can be used to produce products such as recombinant [[protein]]s, used in [[medical research]],<ref>{{cite book | vauthors = Houdebine LM | title = Target Discovery and Validation Reviews and Protocols | chapter = Transgenic animal models in biomedical research | series = Methods in Molecular Biology | volume = 360 | pages = 163–202 | year = 2007 | pmid = 17172731 | doi = 10.1385/1-59745-165-7:163 | isbn = 978-1-59745-165-9 }}</ref> or be grown in [[agriculture]].<ref>{{cite journal | vauthors = Daniell H, Dhingra A | title = Multigene engineering: dawn of an exciting new era in biotechnology | journal = Current Opinion in Biotechnology | volume = 13 | issue = 2 | pages = 136–41 | date = April 2002 | pmid = 11950565 | pmc = 3481857 | doi = 10.1016/S0958-1669(02)00297-5 }}</ref><ref>{{cite journal | vauthors = Job D | title = Plant biotechnology in agriculture | journal = Biochimie | volume = 84 | issue = 11 | pages = 1105–10 | date = November 2002 | pmid = 12595138 | doi = 10.1016/S0300-9084(02)00013-5 }}</ref>
=== DNA profiling ===
{{further|DNA profiling}}
[[Forensic science|Forensic scientists]] can use DNA in [[blood]], [[semen]], [[skin]], [[saliva]] or [[hair]] found at a [[crime scene]] to identify a matching DNA of an individual, such as a perpetrator.<ref>{{Cite news|url=https://theconversation.com/from-the-crime-scene-to-the-courtroom-the-journey-of-a-dna-sample-82250|title=From the crime scene to the courtroom: the journey of a DNA sample| vauthors = Curtis C, Hereward J |date=29 August 2017 |work=The Conversation |access-date=22 October 2017 |archive-url=https://web.archive.org/web/20171022033110/http://theconversation.com/from-the-crime-scene-to-the-courtroom-the-journey-of-a-dna-sample-82250 |archive-date=22 October 2017 |url-status=live }}</ref> This process is formally termed [[DNA profiling]], also called ''DNA fingerprinting''. In DNA profiling, the lengths of variable sections of repetitive DNA, such as [[short tandem repeat]]s and [[minisatellite]]s, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA.<ref>{{cite journal | vauthors = Collins A, Morton NE | title = Likelihood ratios for DNA identification | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 13 | pages = 6007–11 | date = June 1994 | pmid = 8016106 | pmc = 44126 | doi = 10.1073/pnas.91.13.6007 | bibcode = 1994PNAS...91.6007C | doi-access = free }}</ref> However, identification can be complicated if the scene is contaminated with DNA from several people.<ref>{{cite journal | vauthors = Weir BS, Triggs CM, Starling L, Stowell LI, Walsh KA, Buckleton J | title = Interpreting DNA mixtures | journal = Journal of Forensic Sciences | volume = 42 | issue = 2 | pages = 213–22 | date = March 1997 | doi = 10.1520/JFS14100J | pmid = 9068179 | s2cid = 14511630 }}</ref> DNA profiling was developed in 1984 by British geneticist Sir [[Alec Jeffreys]],<ref>{{cite journal | vauthors = Jeffreys AJ, Wilson V, Thein SL | title = Individual-specific 'fingerprints' of human DNA | journal = Nature | volume = 316 | issue = 6023 | pages = 76–79 | year = 1985 | pmid = 2989708 | doi = 10.1038/316076a0 | bibcode = 1985Natur.316...76J | s2cid = 4229883 | doi-access = free }}</ref> and first used in forensic science to convict Colin Pitchfork in the 1988 [[Colin Pitchfork|Enderby murders]] case.<ref>{{Cite web|date=2006-12-14|title=Colin Pitchfork|url=http://www.forensic.gov.uk/forensic_t/inside/news/list_casefiles.php?case=1|access-date=2023-03-27|archive-url=https://web.archive.org/web/20061214004903/http://www.forensic.gov.uk/forensic_t/inside/news/list_casefiles.php?case=1 |archive-date=14 December 2006 }}</ref>
The development of forensic science and the ability to now obtain genetic matching on minute samples of blood, skin, saliva, or hair has led to re-examining many cases. Evidence can now be uncovered that was scientifically impossible at the time of the original examination. Combined with the removal of the [[double jeopardy]] law in some places, this can allow cases to be reopened where prior trials have failed to produce sufficient evidence to convince a jury. People charged with serious crimes may be required to provide a sample of DNA for matching purposes. The most obvious defense to DNA matches obtained forensically is to claim that cross-contamination of evidence has occurred. This has resulted in meticulous strict handling procedures with new cases of serious crime.
DNA profiling is also used successfully to positively identify victims of mass casualty incidents,<ref>{{cite web|url=http://massfatality.dna.gov/Introduction/ |title=DNA Identification in Mass Fatality Incidents |date=September 2006 |publisher=National Institute of Justice |url-status=dead |archive-url=https://web.archive.org/web/20061112000837/http://massfatality.dna.gov/Introduction/ |archive-date=12 November 2006 }}</ref> bodies or body parts in serious accidents, and individual victims in mass war graves, via matching to family members.
DNA profiling is also used in [[DNA paternity testing]] to determine if someone is the biological parent or grandparent of a child with the probability of parentage is typically 99.99% when the alleged parent is biologically related to the child. Normal [[DNA sequencing]] methods happen after birth, but there are new methods to test paternity while a mother is still pregnant.<ref>{{Cite news| vauthors = Pollack A |date=2012-06-19|title=Before Birth, Dad's ID|language=en-US|work=The New York Times|url=https://www.nytimes.com/2012/06/20/health/paternity-blood-tests-that-work-early-in-a-pregnancy.html|access-date=2023-03-27|issn=0362-4331|archive-url=https://web.archive.org/web/20170624231639/http://www.nytimes.com/2012/06/20/health/paternity-blood-tests-that-work-early-in-a-pregnancy.html|archive-date=2017-06-24|url-status=live}}</ref>
=== DNA enzymes or catalytic DNA ===
{{further|Deoxyribozyme}}
[[Deoxyribozyme]]s, also called DNAzymes or catalytic DNA, were first discovered in 1994.<ref name="Breaker 223–229">{{cite journal | vauthors = Breaker RR, Joyce GF | title = A DNA enzyme that cleaves RNA | journal = Chemistry & Biology | volume = 1 | issue = 4 | pages = 223–29 | date = December 1994 | pmid = 9383394 | doi = 10.1016/1074-5521(94)90014-0 }}</ref> They are mostly single stranded DNA sequences isolated from a large pool of random DNA sequences through a combinatorial approach called [[in vitro]] selection or [[systematic evolution of ligands by exponential enrichment]] (SELEX). DNAzymes catalyze variety of chemical reactions including RNA-DNA cleavage, RNA-DNA ligation, amino acids phosphorylation-dephosphorylation, carbon-carbon bond formation, etc. DNAzymes can enhance catalytic rate of chemical reactions up to 100,000,000,000-fold over the uncatalyzed reaction.<ref>{{cite journal | vauthors = Chandra M, Sachdeva A, Silverman SK | title = DNA-catalyzed sequence-specific hydrolysis of DNA | journal = Nature Chemical Biology | volume = 5 | issue = 10 | pages = 718–20 | date = October 2009 | pmid = 19684594 | pmc = 2746877 | doi = 10.1038/nchembio.201 }}</ref> The most extensively studied class of DNAzymes is RNA-cleaving types which have been used to detect different metal ions and designing therapeutic agents. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead-specific),<ref name="Breaker 223–229" /> the CA1-3 DNAzymes (copper-specific),<ref>{{cite journal | vauthors = Carmi N, Shultz LA, Breaker RR | title = In vitro selection of self-cleaving DNAs | journal = Chemistry & Biology | volume = 3 | issue = 12 | pages = 1039–46 | date = December 1996 | pmid = 9000012 | doi = 10.1016/S1074-5521(96)90170-2 | doi-access = free }}</ref> the 39E DNAzyme (uranyl-specific) and the NaA43 DNAzyme (sodium-specific).<ref>{{cite journal | vauthors = Torabi SF, Wu P, McGhee CE, Chen L, Hwang K, Zheng N, Cheng J, Lu Y | title = In vitro selection of a sodium-specific DNAzyme and its application in intracellular sensing | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 19 | pages = 5903–08 | date = May 2015 | pmid = 25918425 | pmc = 4434688 | doi = 10.1073/pnas.1420361112 | bibcode = 2015PNAS..112.5903T | doi-access = free }}</ref> The NaA43 DNAzyme, which is reported to be more than 10,000-fold selective for sodium over other metal ions, was used to make a real-time sodium sensor in cells.
=== Bioinformatics ===
{{further|Bioinformatics}}
[[Bioinformatics]] involves the development of techniques to store, [[data mining|data mine]], search and manipulate biological data, including DNA [[nucleic acid sequence]] data. These have led to widely applied advances in [[computer science]], especially [[string searching algorithm]]s, [[machine learning]], and [[database theory]].<ref>{{cite book | vauthors = Baldi P, Brunak S |author1-link=Pierre Baldi |title=Bioinformatics: The Machine Learning Approach |publisher= MIT Press |year=2001| isbn=978-0-262-02506-5 |oclc=45951728}}</ref> String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides.<ref>{{cite book | vauthors = Gusfield D | title = Algorithms on Strings, Trees, and Sequences: Computer Science and Computational Biology | publisher = [[Cambridge University Press]] | date = 15 January 1997 | isbn = 978-0-521-58519-4 }}</ref> The DNA sequence may be [[sequence alignment|aligned]] with other DNA sequences to identify [[Sequence homology|homologous sequences]] and locate the specific [[mutation]]s that make them distinct. These techniques, especially [[multiple sequence alignment]], are used in studying [[phylogenetics|phylogenetic]] relationships and protein function.<ref>{{cite journal | vauthors = Sjölander K | title = Phylogenomic inference of protein molecular function: advances and challenges | journal = Bioinformatics | volume = 20 | issue = 2 | pages = 170–79 | date = January 2004 | pmid = 14734307 | doi = 10.1093/bioinformatics/bth021 | citeseerx = 10.1.1.412.943 }}</ref> Data sets representing entire genomes' worth of DNA sequences, such as those produced by the [[Human Genome Project]], are difficult to use without the annotations that identify the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by [[Gene prediction|gene finding]] algorithms, which allow researchers to predict the presence of particular [[gene product]]s and their possible functions in an organism even before they have been isolated experimentally.<ref name="Mount">{{cite book | vauthors = Mount DM |title=Bioinformatics: Sequence and Genome Analysis |edition= 2nd |publisher= Cold Spring Harbor Laboratory Press |year= 2004 |isbn= 0-87969-712-1|oclc= 55106399|location=Cold Spring Harbor, NY}}</ref> Entire genomes may also be compared, which can shed light on the evolutionary history of particular organism and permit the examination of complex evolutionary events.
=== DNA nanotechnology ===
{{further|DNA nanotechnology}}
[[File:DNA nanostructures.png|thumb|upright=1.8|The DNA structure at left (schematic shown) will self-assemble into the structure visualized by [[Atomic force microscope|atomic force microscopy]] at right. [[DNA nanotechnology]] is the field that seeks to design nanoscale structures using the [[molecular recognition]] properties of DNA molecules.<ref>{{cite journal | vauthors = Strong M | title = Protein nanomachines | journal = PLOS Biology | volume = 2 | issue = 3 | pages = E73 | date = March 2004 | pmid = 15024422 | pmc = 368168 | doi = 10.1371/journal.pbio.0020073 | s2cid = 13222080 | doi-access = free }}</ref>]]
DNA nanotechnology uses the unique [[molecular recognition]] properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties.<ref>{{cite journal | vauthors = Rothemund PW | s2cid = 4316391 | title = Folding DNA to create nanoscale shapes and patterns | journal = Nature | volume = 440 | issue = 7082 | pages = 297–302 | date = March 2006 | pmid = 16541064 | doi = 10.1038/nature04586 | bibcode = 2006Natur.440..297R | url = https://authors.library.caltech.edu/22244/3/nature04586-s2.pdf }}</ref> DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based and using the ''[[DNA origami]]'' method) and three-dimensional structures in the shapes of [[Polyhedron|polyhedra]].<ref>{{cite journal | vauthors = Andersen ES, Dong M, Nielsen MM, Jahn K, Subramani R, Mamdouh W, Golas MM, Sander B, Stark H, Oliveira CL, Pedersen JS, Birkedal V, Besenbacher F, Gothelf KV, Kjems J | s2cid = 4430815 | title = Self-assembly of a nanoscale DNA box with a controllable lid | journal = Nature | volume = 459 | issue = 7243 | pages = 73–76 | date = May 2009 | pmid = 19424153 | doi = 10.1038/nature07971 | bibcode = 2009Natur.459...73A | hdl = 11858/00-001M-0000-0010-9362-B | hdl-access = free }}</ref> [[DNA machine|Nanomechanical devices]] and [[DNA computing|algorithmic self-assembly]] have also been demonstrated,<ref>{{cite journal | vauthors = Ishitsuka Y, Ha T | title = DNA nanotechnology: a nanomachine goes live | journal = Nature Nanotechnology | volume = 4 | issue = 5 | pages = 281–82 | date = May 2009 | pmid = 19421208 | doi = 10.1038/nnano.2009.101 | bibcode = 2009NatNa...4..281I }}</ref> and these DNA structures have been used to template the arrangement of other molecules such as [[Colloidal gold|gold nanoparticles]] and [[streptavidin]] proteins.<ref>{{cite journal | vauthors = Aldaye FA, Palmer AL, Sleiman HF | title = Assembling materials with DNA as the guide | journal = Science | volume = 321 | issue = 5897 | pages = 1795–99 | date = September 2008 | pmid = 18818351 | doi = 10.1126/science.1154533 | bibcode = 2008Sci...321.1795A | s2cid = 2755388 }}</ref> DNA and other nucleic acids are the basis of [[aptamers]], synthetic oligonucleotide ligands for specific target molecules used in a range of biotechnology and biomedical applications.<ref>{{cite journal | vauthors = Dunn MR, Jimenez RM, Chaput JC |title=Analysis of aptamer discovery and technology |journal=Nature Reviews Chemistry |date=2017 |volume=1 |issue=10 |doi=10.1038/s41570-017-0076 |url=https://www.nature.com/articles/s41570-017-0076 |access-date=30 June 2022}}</ref>
=== History and anthropology ===
{{further|Phylogenetics|Genetic genealogy}}
Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their [[Phylogenetics|phylogeny]].<ref>{{cite journal | vauthors = Wray GA | title = Dating branches on the tree of life using DNA | journal = Genome Biology | volume = 3 | issue = 1 | pages = REVIEWS0001 | year = 2002 | pmid = 11806830 | pmc = 150454 | doi = 10.1186/gb-2001-3-1-reviews0001 | doi-access = free }}</ref> This field of phylogenetics is a powerful tool in [[evolutionary biology]]. If DNA sequences within a species are compared, [[population genetics|population geneticists]] can learn the history of particular populations. This can be used in studies ranging from [[ecological genetics]] to [[anthropology]].
=== Information storage ===
{{Main|DNA digital data storage}}
DNA as a [[data storage|storage device]] for information has enormous potential since it has much higher [[storage density]] compared to electronic devices. However, high costs, slow read and write times ([[memory latency]]), and insufficient [[data corruption|reliability]] has prevented its practical use.<ref name="pmid29744271">{{cite journal | vauthors = Panda D, Molla KA, Baig MJ, Swain A, Behera D, Dash M | title = DNA as a digital information storage device: hope or hype? | journal = 3 Biotech | volume = 8 | issue = 5 | pages = 239 | date = May 2018 | pmid = 29744271 | doi = 10.1007/s13205-018-1246-7 | pmc=5935598}}</ref><ref name="pmid30073589">{{cite journal | vauthors = Akram F, Haq IU, Ali H, Laghari AT | s2cid = 51905843 | title = Trends to store digital data in DNA: an overview | journal = Molecular Biology Reports | volume = 45 | issue = 5 | pages = 1479–1490 | date = October 2018 | pmid = 30073589 | doi = 10.1007/s11033-018-4280-y }}</ref>
== History ==
{{anchor|History of DNA research}}
{{further|History of molecular biology}}
[[File:Maclyn McCarty with Francis Crick and James D Watson - 10.1371 journal.pbio.0030341.g001-O.jpg|thumb|[[Maclyn McCarty]] (left) shakes hands with [[Francis Crick]] and [[James Watson]], co-originators of the double-helix model based on the X-ray diffraction data and insights of [[Rosalind Franklin]] and [[Raymond Gosling]].]]
DNA was first isolated by the Swiss physician [[Friedrich Miescher]] who, in 1869, discovered a microscopic substance in the [[pus]] of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein".<ref>{{cite journal | vauthors = Miescher F | year = 1871 | url = https://books.google.com/books?id=YJRTAAAAcAAJ&pg=PA441 | title = Ueber die chemische Zusammensetzung der Eiterzellen | language = de | trans-title = On the chemical composition of pus cells | journal = Medicinisch-chemische Untersuchungen | volume = 4 | pages = 441–60 | quote = [p. 456] ''Ich habe mich daher später mit meinen Versuchen an die ganzen Kerne gehalten, die Trennung der Körper, die ich einstweilen ohne weiteres Präjudiz als lösliches und unlösliches Nuclein bezeichnen will, einem günstigeren Material überlassend.'' (Therefore, in my experiments I subsequently limited myself to the whole nucleus, leaving to a more favorable material the separation of the substances, that for the present, without further prejudice, I will designate as soluble and insoluble nuclear material ("Nuclein"))}}</ref><ref>{{cite journal | vauthors = Dahm R | s2cid = 915930 | title = Discovering DNA: Friedrich Miescher and the early years of nucleic acid research | journal = Human Genetics | volume = 122 | issue = 6 | pages = 565–81 | date = January 2008 | pmid = 17901982 | doi = 10.1007/s00439-007-0433-0 }}</ref> In 1878, [[Albrecht Kossel]] isolated the non-protein component of "nuclein", nucleic acid, and later isolated its five primary [[nucleobase]]s.<ref>See:
* {{cite journal | vauthors = Kossel A | year = 1879 | url = https://books.google.com/books?id=4H5NAAAAYAAJ&pg=PA284 | title = Ueber Nucleïn der Hefe | language = de| trans-title = On nuclein in yeast | journal = Zeitschrift für physiologische Chemie | volume = 3 | pages = 284–91 }}
* {{cite journal | vauthors = Kossel A | year = 1880 | url = https://books.google.com/books?id=u4s1AQAAMAAJ&pg=PA290 | title = Ueber Nucleïn der Hefe II | language = de | trans-title = On nuclein in yeast, Part 2 | journal = Zeitschrift für physiologische Chemie | volume = 4 | pages = 290–95 }}
* {{cite journal | vauthors = Kossel A | year = 1881 | url = https://books.google.com/books?id=xYs1AQAAMAAJ&pg=PA267 | title = Ueber die Verbreitung des Hypoxanthins im Thier- und Pflanzenreich | language = de | trans-title = On the distribution of hypoxanthins in the animal and plant kingdoms | journal = Zeitschrift für physiologische Chemie | volume = 5 | pages = 267–71 }}
* {{cite book | vauthors = Kossel A | title = Untersuchungen über die Nucleine und ihre Spaltungsprodukte | language = de | trans-title = Investigations into nuclein and its cleavage products | location = Strassburg, Germany | publisher = K.J. Trübner | year = 1881 | pages = 19 }}
* {{cite journal | vauthors = Kossel A | year = 1882 | url = https://books.google.com/books?id=z4s1AQAAMAAJ&pg=PA422 | title = Ueber Xanthin und Hypoxanthin |trans-title= On xanthin and hypoxanthin | journal = Zeitschrift für physiologische Chemie | volume = 6 | pages = 422–31 }}
* Albrect Kossel (1883) [https://books.google.com/books?id=2os1AQAAMAAJ&pg=PA7 "Zur Chemie des Zellkerns"] {{webarchive|url=https://web.archive.org/web/20171117235430/https://books.google.com/books?id=2os1AQAAMAAJ&pg=PA7 |date=17 November 2017 }} (On the chemistry of the cell nucleus), ''Zeitschrift für physiologische Chemie'', '''7''': 7–22.
* {{cite journal | vauthors = Kossel A | year = 1886 | title = Weitere Beiträge zur Chemie des Zellkerns | language = de | trans-title = Further contributions to the chemistry of the cell nucleus | journal = Zeitschrift für Physiologische Chemie | volume = 10 | pages = 248–64 | url = http://vlp.mpiwg-berlin.mpg.de/library/data/lit16615/index_html?pn=1&ws=1.5 | quote = On p. 264, Kossel remarked presciently: Der Erforschung der quantitativen Verhältnisse der vier stickstoffreichen Basen, der Abhängigkeit ihrer Menge von den physiologischen Zuständen der Zelle, verspricht wichtige Aufschlüsse über die elementaren physiologisch-chemischen Vorgänge. (The study of the quantitative relations of the four nitrogenous bases—[and] of the dependence of their quantity on the physiological states of the cell—promises important insights into the fundamental physiological-chemical processes.) }}</ref><ref name="Yale_Jones_1953">{{cite journal | vauthors = Jones ME | title = Albrecht Kossel, a biographical sketch | journal = The Yale Journal of Biology and Medicine | volume = 26 | issue = 1 | pages = 80–97 | date = September 1953 | pmid = 13103145 | pmc = 2599350 }}</ref>
In 1909, [[Phoebus Levene]] identified the base, sugar, and phosphate nucleotide unit of RNA (then named "yeast nucleic acid").<ref>{{cite journal | vauthors = Levene PA, Jacobs WA | year = 1909 | title = Über Inosinsäure | language = de | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 42 | pages = 1198–203 |url=https://babel.hathitrust.org/cgi/pt?id=iau.31858002459620&view=1up&seq=1054 | doi=10.1002/cber.190904201196}}</ref><ref>{{cite journal | vauthors = Levene PA, Jacobs WA | year = 1909 | title = Über die Hefe-Nucleinsäure | language = de | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 42 | issue = 2 | pages = 2474–78 | doi=10.1002/cber.190904202148| url = https://zenodo.org/record/2175598 }}</ref><ref>{{cite journal | vauthors = Levene P |title=The structure of yeast nucleic acid| journal=J Biol Chem |volume=40 |issue=2 |pages=415–24 |year=1919|doi=10.1016/S0021-9258(18)87254-4|doi-access=free }}</ref> In 1929, Levene identified deoxyribose sugar in "thymus nucleic acid" (DNA).<ref>{{cite journal | vauthors = Cohen JS, Portugal FH | year = 1974 | title = The search for the chemical structure of DNA | journal = Connecticut Medicine | volume = 38 | issue = 10 | pages = 551–52, 554–57 | pmid = 4609088 | url = https://profiles.nlm.nih.gov/ps/access/CCAAHW.pdf }}</ref> Levene suggested that DNA consisted of a string of four nucleotide units linked together through the phosphate groups ("tetranucleotide hypothesis"). Levene thought the chain was short and the bases repeated in a fixed order. In 1927, [[Nikolai Koltsov]] proposed that inherited traits would be inherited via a "giant hereditary molecule" made up of "two mirror strands that would replicate in a semi-conservative fashion using each strand as a template".<ref>Koltsov proposed that a cell's genetic information was encoded in a long chain of amino acids. See:
* {{cite speech | vauthors = Koltsov HK | title = Физико-химические основы морфологии | trans-title = The physical-chemical basis of morphology | language = ru | event = 3rd All-Union Meeting of Zoologist, Anatomists, and Histologists | location = Leningrad, U.S.S.R. | date = 12 December 1927 }}
* Reprinted in: {{cite journal | vauthors = Koltsov HK | title = Физико-химические основы морфологии | trans-title = The physical-chemical basis of morphology | language = ru| journal = Успехи экспериментальной биологии (Advances in Experimental Biology) series B | volume = 7 | issue = 1 | pages = ? | date = 1928 }}
* Reprinted in German as: {{cite journal | vauthors = Koltzoff NK | date = 1928 | title = Physikalisch-chemische Grundlagen der Morphologie | trans-title = The physical-chemical basis of morphology | language = de | journal = Biologisches Zentralblatt | volume = 48 | issue = 6 | pages = 345–69 }}
* In 1934, Koltsov contended that the proteins that contain a cell's genetic information replicate. See: {{cite journal | vauthors = Koltzoff N | title = The structure of the chromosomes in the salivary glands of Drosophila | journal = Science | volume = 80 | issue = 2075 | pages = 312–13 | date = October 1934 | pmid = 17769043 | doi = 10.1126/science.80.2075.312 | quote = From page 313: "I think that the size of the chromosomes in the salivary glands [of Drosophila] is determined through the multiplication of ''genonemes''. By this term I designate the axial thread of the chromosome, in which the geneticists locate the linear combination of genes; … In the normal chromosome there is usually only one genoneme; before cell-division this genoneme has become divided into two strands."| bibcode = 1934Sci....80..312K }}</ref><ref name="Soyfer">{{cite journal | vauthors = Soyfer VN | s2cid = 46277758 | title = The consequences of political dictatorship for Russian science | journal = Nature Reviews Genetics | volume = 2 | issue = 9 | pages = 723–29 | date = September 2001 | pmid = 11533721 | doi = 10.1038/35088598 }}</ref> In 1928, [[Frederick Griffith]] in his [[Griffith's experiment|experiment]] discovered that [[trait (biology)|traits]] of the "smooth" form of ''Pneumococcus'' could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form.<ref>{{cite journal | vauthors = Griffith F | title = The Significance of Pneumococcal Types | journal = The Journal of Hygiene | volume = 27 | issue = 2 | pages = 113–59 | date = January 1928 | pmid = 20474956 | pmc = 2167760 | doi = 10.1017/S0022172400031879 }}</ref><ref>{{cite journal | vauthors = Lorenz MG, Wackernagel W | title = Bacterial gene transfer by natural genetic transformation in the environment | journal = Microbiological Reviews | volume = 58 | issue = 3 | pages = 563–602 | date = September 1994 | pmid = 7968924 | pmc = 372978 | doi = 10.1128/MMBR.58.3.563-602.1994 }}</ref> This system provided the first clear suggestion that DNA carries genetic information.
In 1933, while studying virgin [[sea urchin]] eggs, [[Jean Brachet]] suggested that DNA is found in the [[cell nucleus]] and that [[RNA]] is present exclusively in the [[cytoplasm]]. At the time, "yeast nucleic acid" (RNA) was thought to occur only in plants, while "thymus nucleic acid" (DNA) only in animals. The latter was thought to be a tetramer, with the function of buffering cellular pH.<ref>{{cite journal | vauthors = Brachet J | year = 1933 | title = Recherches sur la synthese de l'acide thymonucleique pendant le developpement de l'oeuf d'Oursin | language = it | journal = Archives de Biologie | volume = 44 | pages = 519–76 }}</ref><ref>{{cite book | vauthors = Burian R | year = 1994 | chapter = Jean Brachet's Cytochemical Embryology: Connections with the Renovation of Biology in France? | veditors = Debru C, Gayon J, Picard JF | title = Les sciences biologiques et médicales en France 1920–1950 | volume = 2 | series = Cahiers pour I'histoire de la recherche | location = Paris | publisher = CNRS Editions | pages = 207–20 | chapter-url = http://www.histcnrs.fr/ColloqDijon/Burian-Brachet.pdf }}</ref>
In 1937, [[William Astbury]] produced the first X-ray diffraction patterns that showed that DNA had a regular structure.<ref>See:
* {{cite journal | vauthors = Astbury WT, Bell FO | year = 1938 | title = Some recent developments in the X-ray study of proteins and related structures | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 6 | pages = 109–21 | url = http://www.leeds.ac.uk/heritage/Astbury/bibliography/CSHSQB_Astbury_and_Bell_1938.pdf | archive-url = https://web.archive.org/web/20140714204539/http://www.leeds.ac.uk/heritage/Astbury/bibliography/CSHSQB_Astbury_and_Bell_1938.pdf | archive-date = 14 July 2014 | doi=10.1101/sqb.1938.006.01.013}}
* {{cite journal | vauthors = Astbury WT | title = X-ray studies of nucleic acids | journal = Symposia of the Society for Experimental Biology | issue = 1 | pages = 66–76 | year = 1947 | pmid = 20257017 | url = http://scarc.library.oregonstate.edu/coll/pauling/dna/papers/astbury-xray.html | archive-url = https://web.archive.org/web/20140705132403/http://scarc.library.oregonstate.edu/coll/pauling/dna/papers/astbury-xray.html | archive-date=5 July 2014 }}</ref>
In 1943, [[Oswald Avery]], along with co-workers [[Colin Munro MacLeod|Colin MacLeod]] and [[Maclyn McCarty]], identified DNA as the [[Griffith's experiment|transforming principle]], supporting Griffith's suggestion ([[Avery–MacLeod–McCarty experiment]]).<ref>{{cite journal | vauthors = Avery OT, Macleod CM, McCarty M | title = Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III | journal = The Journal of Experimental Medicine | volume = 79 | issue = 2 | pages = 137–158 | date = February 1944 | pmid = 19871359 | pmc = 2135445 | doi = 10.1084/jem.79.2.137 }}</ref> [[Erwin Chargaff]] developed and published observations now known as [[Chargaff's rules]], stating that in DNA from any species of any organism, the amount of [[guanine]] should be equal to [[cytosine]] and the amount of [[adenine]] should be equal to [[thymine]].<ref name="chargaff_1950">{{cite journal | vauthors = Chargaff E | title = Chemical specificity of nucleic acids and mechanism of their enzymatic degradation | journal = Experientia | volume = 6 | issue = 6 | pages = 201–209 | date = June 1950 | pmid = 15421335 | doi = 10.1007/BF02173653 | s2cid = 2522535 }}</ref><ref name="kresge_2005">{{cite journal | vauthors = Kresge N, Simoni RD, Hill RL |title=Chargaff's Rules: the Work of Erwin Chargaff |journal=Journal of Biological Chemistry |date=June 2005 |volume=280 |issue=24 |pages=172–174 |doi=10.1016/S0021-9258(20)61522-8|doi-access=free }}</ref>
[[File:TheEaglePub-Cambridge-BluePlaque.jpg|thumb|left|A [[blue plaque]] outside [[The Eagle, Cambridge|The Eagle]] [[pub]] in Cambridge, England commemorating Crick and Watson]]
Late in 1951, [[Francis Crick]] started working with [[James Watson]] at the [[Cavendish Laboratory]] within the [[University of Cambridge]]. DNA's role in [[heredity]] was confirmed in 1952 when [[Alfred Hershey]] and [[Martha Chase]] in the [[Hershey–Chase experiment]] showed that DNA is the [[genetic material]] of the [[enterobacteria phage T2]].<ref>{{cite journal | vauthors = Hershey AD, Chase M | title = Independent functions of viral protein and nucleic acid in growth of bacteriophage | journal = The Journal of General Physiology | volume = 36 | issue = 1 | pages = 39–56 | date = May 1952 | pmid = 12981234 | pmc = 2147348 | doi = 10.1085/jgp.36.1.39 }}</ref>
In May 1952, [[Raymond Gosling]], a graduate student working under the supervision of [[Rosalind Franklin]], took an [[X-ray diffraction]] image, labeled as "[[Photo 51]]",<ref>{{Cite web|title=Pictures and Illustrations: Crystallographic photo of Sodium Thymonucleate, Type B. "Photo 51." May 1952|url=http://scarc.library.oregonstate.edu/coll/pauling/dna/pictures/sci9.001.5.html|access-date=2023-05-18|website=scarc.library.oregonstate.edu}}</ref> at high hydration levels of DNA. This photo was given to Watson and Crick by [[Maurice Wilkins]] and was critical to their obtaining the correct structure of DNA. Franklin told Crick and Watson that the backbones had to be on the outside. Before then, Linus Pauling, and Watson and Crick, had erroneous models with the chains inside and the bases pointing outwards. Franklin's identification of the [[space group]] for DNA crystals revealed to Crick that the two DNA strands were [[Antiparallel (biochemistry)|antiparallel]].<ref name="ReferenceA">{{cite book| vauthors = Schwartz J |title=In pursuit of the gene: from Darwin to DNA |url= https://archive.org/details/inpursuitofgenef00schw |url-access=registration |year=2008|publisher=Harvard University Press|location=Cambridge, Mass.|isbn=978-0-674-02670-4 }}</ref> In February 1953, [[Linus Pauling]] and [[Robert Corey]] proposed a model for nucleic acids containing three intertwined chains, with the phosphates near the axis, and the bases on the outside.<ref name="pmid16578429">{{cite journal | vauthors = Pauling L, Corey RB | title = A Proposed Structure For The Nucleic Acids | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 39 | issue = 2 | pages = 84–97 | date = February 1953 | pmid = 16578429 | pmc = 1063734 | doi = 10.1073/pnas.39.2.84| url = http://scarc.library.oregonstate.edu/coll/pauling/dna/papers/1953p.9-084.html | bibcode = 1953PNAS...39...84P | doi-access = free }}</ref> Watson and Crick completed their model, which is now accepted as the first correct model of the double helix of [[Molecular structure of Nucleic Acids|DNA]]. On 28 February 1953 Crick interrupted patrons' lunchtime at [[The Eagle, Cambridge|The Eagle]] [[pub]] in Cambridge, England to announce that he and Watson had "discovered the secret of life".<ref>{{cite book | vauthors = Regis E | date = 2009 | title = What Is Life?: investigating the nature of life in the age of synthetic biology | location = Oxford | publisher = [[Oxford University Press]] | isbn = 978-0-19-538341-6 | page = 52 }}</ref>
[[File:Pencil sketch of the DNA double helix by Francis Crick Wellcome L0051225.jpg|thumb|upright|Pencil sketch of the DNA double helix by Francis Crick in 1953]]
The 25 April 1953 issue of the journal ''[[Nature (journal)|Nature]]'' published a series of five articles giving the Watson and Crick double-helix structure DNA and evidence supporting it.<ref name=NatureDNA50>{{cite web | work = Nature Archives | url = http://www.nature.com/nature/dna50/archive.html | title = Double Helix of DNA: 50 Years | archive-url = https://web.archive.org/web/20150405140401/http://www.nature.com/nature/dna50/archive.html | archive-date=5 April 2015 | url-status=dead }}</ref> The structure was reported in a letter titled "''MOLECULAR STRUCTURE OF NUCLEIC ACIDS A Structure for Deoxyribose Nucleic Acid''{{-"}}, in which they said, "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."<ref name="Watson-1953" /> This letter was followed by a letter from Franklin and Gosling, which was the first publication of their own X-ray diffraction data and of their original analysis method.<ref name=NatFranGos /><ref>{{cite web | url = http://osulibrary.oregonstate.edu/specialcollections/coll/pauling/dna/pictures/franklin-typeBphoto.html | title = Original X-ray diffraction image | publisher = Oregon State Library | access-date = 6 February 2011 | url-status=live | archive-url = https://web.archive.org/web/20090130111849/http://osulibrary.oregonstate.edu/specialcollections/coll/pauling/dna/pictures/franklin-typeBphoto.html | archive-date=30 January 2009 }}</ref> Then followed a letter by Wilkins and two of his colleagues, which contained an analysis of ''in vivo'' B-DNA X-ray patterns, and which supported the presence ''in vivo'' of the Watson and Crick structure.<ref name="NatWilk" />
In April 2023, scientists, based on new evidence, concluded that Rosalind Franklin was a contributor and "equal player" in the discovery process of DNA, rather than otherwise, as may have been presented subsequently after the time of the discovery.<ref name="AP-20230425">{{cite news | vauthors = Burakoff M |title=Rosalind Franklin's role in DNA discovery gets a new twist |url=https://apnews.com/article/dna-double-helix-rosalind-franklin-watson-crick-69ec8164c720e0b23374da69a1d3708d |date=25 April 2023 |work=[[AP News]] |accessdate=25 April 2023 }}</ref><ref name="NYT-20230425">{{cite news | vauthors = Anthes E |title=Untangling Rosalind Franklin's Role in DNA Discovery, 70 Years On – Historians have long debated the role that Dr. Franklin played in identifying the double helix. A new opinion essay argues that she was an "equal contributor." |url=https://www.nytimes.com/2023/04/25/science/rosalind-franklin-dna.html |date=25 April 2023 |work=[[The New York Times]] |url-status=live |archiveurl=https://archive.today/20230425182515/https://www.nytimes.com/2023/04/25/science/rosalind-franklin-dna.html |archivedate=25 April 2023 |accessdate=26 April 2023 }}</ref><ref name="NAT-202304254">{{cite journal | vauthors = Cobb M, Comfort N |title=What Rosalind Franklin truly contributed to the discovery of DNA's structure – Franklin was no victim in how the DNA double helix was solved. An overlooked letter and an unpublished news article, both written in 1953, reveal that she was an equal player. |date=25 April 2023 |journal=[[Nature (journal)|Nature]] |volume=616 |issue=7958 |pages=657–660 |doi=10.1038/d41586-023-01313-5 |pmid=37100935 |s2cid=258314143 |doi-access=free |bibcode=2023Natur.616..657C }}</ref>
In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the [[Nobel Prize in Physiology or Medicine]].<ref>{{cite web | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1962/ | title = The Nobel Prize in Physiology or Medicine 1962 | work = Nobelprize.org }}</ref> Nobel Prizes are awarded only to living recipients. A debate continues about who should receive credit for the discovery.<ref>{{cite journal | vauthors = Maddox B | s2cid = 4428347 | title = The double helix and the 'wronged heroine' | journal = Nature | volume = 421 | issue = 6921 | pages = 407–08 | date = January 2003 | pmid = 12540909 | doi = 10.1038/nature01399 | url = http://www.biomath.nyu.edu/index/course/hw_articles/nature4.pdf | bibcode = 2003Natur.421..407M | url-status=live | archive-url = https://web.archive.org/web/20161017011403/http://www.biomath.nyu.edu/index/course/hw_articles/nature4.pdf | archive-date = 17 October 2016 | df = dmy-all | doi-access = free }}</ref>
In an influential presentation in 1957, Crick laid out the [[central dogma of molecular biology]], which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis".<ref>{{cite speech | vauthors = Crick FH |title=A Note for the RNA Tie Club | date= 1955 | location = Cambridge, England |url= http://genome.wellcome.ac.uk/assets/wtx030893.pdf | archive-url = https://web.archive.org/web/20081001223217/http://genome.wellcome.ac.uk/assets/wtx030893.pdf | url-status=dead | archive-date = 1 October 2008 }}</ref> Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the [[Meselson–Stahl experiment]].<ref>{{cite journal | vauthors = Meselson M, Stahl FW | title = The Replication of DNA in Escherichia Coli | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 44 | issue = 7 | pages = 671–82 | date = July 1958 | pmid = 16590258 | pmc = 528642 | doi = 10.1073/pnas.44.7.671 | bibcode = 1958PNAS...44..671M | doi-access = free }}</ref> Further work by Crick and co-workers showed that the genetic code was based on non-overlapping triplets of bases, called [[Genetic code#Codons|codons]], allowing [[Har Gobind Khorana]], [[Robert W. Holley]], and [[Marshall Warren Nirenberg]] to decipher the genetic code.<ref>{{cite web | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1968/ | title = The Nobel Prize in Physiology or Medicine 1968 | work = Nobelprize.org }}</ref> These findings represent the birth of [[molecular biology]].<ref>{{cite journal | vauthors = Pray L | year = 2008 | title = Discovery of DNA structure and function: Watson and Crick. | journal = Nature Education | volume = 1 | issue = 1 | pages = 100 }}</ref>
{{clear}}
In 1986, DNA analysis was first used for criminal investigative purposes when police in the UK requested [[Alec Jeffreys]] of the University of Leicester to verify or disprove a suspect's rape-murder "confession". In this particular case, the suspect had confessed to two rape-murders, but had later retracted his confession. DNA testing at the university labs soon disproved the veracity of the suspect's original "confession", and the suspect was exonerated from the murder-rape charges.<ref>{{cite journal | pmc=3561883 | year=2003 | vauthors=Panneerchelvam S, Norazmi MN | title=Forensic DNA Profiling and Database | journal=The Malaysian Journal of Medical Sciences | volume=10 | issue=2 | pages=20–26 | pmid=23386793 }}</ref>
== See also ==
{{Div col}}
* {{annotated link|Autosome}}
* {{annotated link|Crystallography}}
* {{annotated link|DNA Day}}
* {{annotated link|DNA microarray}}
* {{annotated link|DNA sequencing}}
* {{annotated link|Genetic disorder}}
* {{annotated link|Genetic genealogy}}
* {{annotated link|Haplotype}}
* {{annotated link|Meiosis}}
* {{annotated link|Nucleic acid notation}}
* {{annotated link|Nucleic acid sequence}}
* {{annotated link|Ribosomal DNA}}
* {{annotated link|Southern blot}}
* {{annotated link|X-ray scattering techniques}}
* {{annotated link|Xeno nucleic acid}}
{{Div col end}}
== References ==
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}}
== Further reading ==
{{refbegin}}
* {{cite book | vauthors = Berry A, Watson J | author-link2 = James Watson | name-list-style = vanc | title = DNA: the secret of life | publisher = Alfred A. Knopf | location = New York | year = 2003 | isbn = 0-375-41546-7 | url = https://archive.org/details/dnasecretoflife00wats }}
* {{cite book |title=Understanding DNA: the molecule & how it works | vauthors = Calladine CR, Drew HR, Luisi BF, Travers AA | year = 2003 |publisher=Elsevier Academic Press |location=Amsterdam |isbn=0-12-155089-3}}
* {{cite book | vauthors = Carina D, Clayton J | title = 50 years of DNA | publisher = Palgrave Macmillan | location = Basingstoke | year = 2003 | isbn = 1-4039-1479-6 | url = https://archive.org/details/50yearsofdna00clay }}
* {{cite book | author-link = Horace Freeland Judson | vauthors = Judson HF | date = 1979 | title = The Eighth Day of Creation: Makers of the Revolution in Biology | isbn = 0-671-22540-5 | edition = 2nd | publisher = Cold Spring Harbor Laboratory Press }}
* {{cite book | vauthors = Olby RC | author-link = Robert Olby | title = The path to the double helix: the discovery of DNA |publisher=Dover Publications |location=New York |year=1994 |isbn=0-486-68117-3}} First published in October 1974 by MacMillan, with foreword by Francis Crick; the definitive DNA textbook, revised in 1994 with a nine-page postscript.
* {{cite journal | vauthors = Olby R | title = Quiet debut for the double helix | journal = Nature | volume = 421 | issue = 6921 | pages = 402–05 | date = January 2003 | pmid = 12540907 | doi = 10.1038/nature01397 | author-link = Robert Olby | bibcode = 2003Natur.421..402O | doi-access = free }}
* {{cite book | vauthors = Olby RC | title=Francis Crick: A Biography |publisher=Cold Spring Harbor Laboratory Press |location=Plainview, N.Y |year=2009 |isbn=978-0-87969-798-3}}
* {{cite book | vauthors = Micklas D | date = 2003 | title = DNA Science: A First Course | publisher = Cold Spring Harbor Press | isbn = 978-0-87969-636-8 }}
* {{cite book | vauthors = Ridley M | author-link = Matt Ridley |title=Francis Crick: discoverer of the genetic code |publisher=Eminent Lives, Atlas Books |location=Ashland, OH |year=2006 |isbn=0-06-082333-X}}
* {{cite book | vauthors = Rosenfeld I | date = 2010 | title = DNA: A Graphic Guide to the Molecule that Shook the World | publisher = Columbia University Press | isbn = 978-0-231-14271-7 }}
* {{cite book | vauthors = Schultz M, Cannon Z | date = 2009 | title = The Stuff of Life: A Graphic Guide to Genetics and DNA | url = https://archive.org/details/stuffoflifegraph00schu | url-access = registration | publisher = Hill and Wang | isbn = 978-0-8090-8947-5 }}
* {{cite book | author-link1 = Gunther Stent | vauthors = Stent GS, Watson J |title=The Double Helix: A Personal Account of the Discovery of the Structure of DNA | url = https://archive.org/details/doublehelixpers00wats_0 | url-access = registration |publisher=Norton |location=New York |year=1980 |isbn=0-393-95075-1}}
* {{cite book | vauthors = Watson J | date = 2004 | title = DNA: The Secret of Life | publisher = Random House | isbn = 978-0-09-945184-6 }}
* {{cite book | author-link = Maurice Wilkins | vauthors = Wilkins M |title=The third man of the double helix the autobiography of Maurice Wilkins |publisher=University Press |location=Cambridge, England |year=2003 |isbn=0-19-860665-6}}
{{refend}}
== External links ==
{{Library resources box
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{{Spoken Wikipedia|dna.ogg|date=12 February 2007}}
* [https://web.archive.org/web/20070306082905/http://pipe.scs.fsu.edu/displar.html DNA binding site prediction on protein]
* [https://web.archive.org/web/20100223035803/http://nobelprize.org/educational_games/medicine/dna_double_helix/ DNA the Double Helix Game] From the official Nobel Prize web site
* [http://www.fidelitysystems.com/Unlinked_DNA.html DNA under electron microscope]
* [http://www.dnalc.org/ Dolan DNA Learning Center]
* [http://www.nature.com/nature/dna50/archive.html Double Helix: 50 years of DNA], ''[[Nature (journal)|Nature]]''
* {{Proteopedia|DNA}}
* {{Proteopedia|Forms_of_DNA}}
* [http://www.nature.com/encode/ ENCODE threads explorer] ENCODE home page at [[Nature (journal)|Nature]]
* [https://web.archive.org/web/20070213030135/http://www.ncbe.reading.ac.uk/DNA50/ Double Helix 1953–2003] National Centre for Biotechnology Education
* [http://www.genome.gov/10506718 Genetic Education Modules for Teachers] – ''DNA from the Beginning'' Study Guide
* {{PDB Molecule of the Month|23|DNA}}
* [https://www.nytimes.com/packages/pdf/science/dna-article.pdf "Clue to chemistry of heredity found"]. ''[[The New York Times]]'', June 1953. First American newspaper coverage of the discovery of the DNA structure
* [http://www.dnaftb.org/ DNA from the Beginning] Another DNA Learning Center site on DNA, genes, and heredity from Mendel to the human genome project.
* [https://web.archive.org/web/20070825101712/http://orpheus.ucsd.edu/speccoll/testing/html/mss0660a.html#abstract The Register of Francis Crick Personal Papers 1938&nbsp;– 2007] at Mandeville Special Collections Library, [[University of California, San Diego]]
* [http://www.nature.com/polopoly_fs/7.9746!/file/Crick%20letter%20to%20Michael.pdf Seven-page, handwritten letter that Crick sent to his 12-year-old son Michael in 1953 describing the structure of DNA.] See [http://www.nature.com/news/crick-s-medal-goes-under-the-hammer-1.12705 Crick's medal goes under the hammer], Nature, 5 April 2013.
{{Genetics}}
{{Gene expression}}
{{Nucleic acids}}
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[[Category:DNA| ]]
[[Category:Biotechnology]]
[[Category:Helices]]
[[Category:Nucleic acids]]