View source for H2AFX

{{Short description|Histone protein from the H2A family}}
{{Infobox gene}}
'''H2A histone family member X''' (usually abbreviated as '''H2AX''') is a type of [[histone]] protein from the [[histone H2A|H2A family]] encoded by the ''H2AFX'' gene. An important phosphorylated form is γH2AX (S139), which forms when double-strand breaks appear.
In humans and other [[eukaryotes]], the [[DNA]] is wrapped around [[histone]] octamers, consisting of [[core histones]] H2A, [[Histone H2B|H2B]], [[Histone H3|H3]] and [[Histone H4|H4]], to form [[chromatin]]. H2AX contributes to [[nucleosome]]-formation, chromatin-remodeling and [[DNA repair]], and is also used ''in vitro'' as an assay for double-strand breaks in [[dsDNA]].
==Formation of γH2AX==
H2AX becomes phosphorylated on serine 139, then called γH2AX, as a reaction on [[DNA repair#Double-strand breaks|DNA double-strand breaks (DSB)]]. The kinases of the PI3-family ([[Ataxia telangiectasia mutated]], [[Ataxia telangiectasia and Rad3 related|ATR]] and DNA-PKcs) are responsible for this phosphorylation, especially ATM. The modification can happen accidentally during replication fork collapse or in the response to ionizing radiation but also during controlled physiological processes such as V(D)J recombination. γH2AX is a sensitive target for looking at DSBs in cells. The presence of γH2AX by itself, however, is not the evidence of the DSBs.<ref>{{cite journal | vauthors = Cleaver JE, Feeney L, Revet I | year = 2011 | title = Phosphorylated H2Ax is not an unambiguous marker for DNA double strand breaks | journal = Cell Cycle | volume = 10 | issue = 19| pages = 3223–4 | pmid = 21921674 | doi = 10.4161/cc.10.19.17448 | doi-access = free }}</ref> The role of the phosphorylated form of the histone in DNA repair is under discussion but it is known that because of the modification the DNA becomes less condensed, potentially allowing space for the recruitment of proteins necessary during repair of DSBs.  Mutagenesis experiments have shown that the modification is necessary for the proper formation of ionizing radiation induced foci in response to double strand breaks, but is not required for the recruitment of proteins to the site of DSBs.
== Function ==
===DNA damage response===
The [[histone]] variant H2AX constitutes about 2-25% of the H2A histones in mammalian chromatin.<ref name="Rogakou 1998">{{cite journal |vauthors=Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM |title=DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139 |journal=J. Biol. Chem. |volume=273 |issue=10 |pages=5858–68 |year=1998 |pmid=9488723 |doi= 10.1074/jbc.273.10.5858|doi-access=free }}</ref>  When a double-strand break occurs in DNA, a sequence of events occurs in which H2AX is altered.
Very early after a double-strand break, a specific protein that interacts with and affects the architecture of chromatin is phosphorylated and then released from the chromatin.  This protein, [[heterochromatin protein 1]] (HP1)-beta ([[CBX1]]), is bound to [[histone H3]] [[histone methylation|methylated]] on lysine 9 (H3K9me). Half-maximum release of HP1-beta from damaged DNA occurs within one second.<ref name=Ayoub2008>{{cite journal |vauthors=Ayoub N, Jeyasekharan AD, Bernal JA, Venkitaraman AR |title=HP1-beta mobilization promotes chromatin changes that initiate the DNA damage response |journal=Nature |volume=453 |issue=7195 |pages=682–6 |year=2008 |pmid=18438399 |doi=10.1038/nature06875 |bibcode=2008Natur.453..682A |s2cid=4348736 }}</ref>  A dynamic alteration in chromatin structure is triggered by HP1-beta release.  This alteration in chromatin structure promotes H2AX phosphorylation by [[ATM serine/threonine kinase|ATM]], [[Ataxia telangiectasia and Rad3 related|ATR]] and [[DNA-PKcs|DNA-PK]],<ref name="pmid12660252">{{cite journal |vauthors=Furuta T, Takemura H, Liao ZY, Aune GJ, Redon C, Sedelnikova OA, Pilch DR, Rogakou EP, Celeste A, Chen HT, Nussenzweig A, Aladjem MI, Bonner WM, Pommier Y |title=Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes |journal=J. Biol. Chem. |volume=278 |issue=22 |pages=20303–12 |year=2003 |pmid=12660252 |doi=10.1074/jbc.M300198200 |doi-access=free }}</ref> allowing formation of γH2AX (H2AX phosphorylated on serine 139).  γH2AX can be detected as soon as 20 seconds after irradiation of cells (with DNA double-strand break formation), and half maximum accumulation of γH2AX occurs in one minute.<ref name="Rogakou 1998" />  Chromatin with phosphorylated γH2AX extends to about a million base pairs on each side of a DNA double-strand break.<ref name="Rogakou 1998" />
[[MDC1]] (mediator of DNA damage checkpoint protein 1) then binds to γH2AX and the γH2AX/MDC1 complex then orchestrates further interactions in double-strand break repair.<ref name=Scully>{{cite journal |vauthors=Scully R, Xie A |title=Double strand break repair functions of histone H2AX |journal=Mutat. Res. |volume=750 |issue=1–2 |pages=5–14 |year=2013 |pmid=23916969 |pmc=3818383 |doi=10.1016/j.mrfmmm.2013.07.007 |bibcode=2013MRFMM.750....5S }}</ref>  The ubiquitin ligases RNF8 and [[RNF168]] bind to the γH2AX/MDC1 complex, ubiquitylating other chromatin components.  This allows the recruitment of BRCA1 and 53BP1 to the long, modified γH2AX/MDC1 chromatin.<ref name=Scully />  Other proteins that stably assemble on the extensive γH2AX-modified chromatin are the [[MRN complex]] (a [[protein complex]] consisting of [[MRE11A|Mre11]], [[Rad50]] and [[Nibrin|Nbs1]]), [[RAD51]] and the [[ATM serine/threonine kinase|ATM kinase]].<ref name="pmid16618811">{{cite journal |vauthors=Bekker-Jensen S, Lukas C, Kitagawa R, Melander F, Kastan MB, Bartek J, Lukas J |title=Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks |journal=J. Cell Biol. |volume=173 |issue=2 |pages=195–206 |year=2006 |pmid=16618811 |pmc=2063811 |doi=10.1083/jcb.200510130 }}</ref><ref name=Essers>{{cite journal |vauthors=Essers J, Houtsmuller AB, van Veelen L, Paulusma C, Nigg AL, Pastink A, Vermeulen W, Hoeijmakers JH, Kanaar R |title=Nuclear dynamics of RAD52 group homologous recombination proteins in response to DNA damage |journal=EMBO J. |volume=21 |issue=8 |pages=2030–7 |year=2002 |pmid=11953322 |pmc=125370 |doi=10.1093/emboj/21.8.2030 }}</ref>  Further DNA repair components, such as RAD52 and RAD54, rapidly and reversibly interact with the core components stably associated with γH2AX-modified chromatin.<ref name=Essers /> The constitutive level of γH2AX expression in live cells, untreated by exogenous agents, likely represents DNA damage by endogenous oxidants generated during cellular respiration.<ref>{{cite journal | vauthors = Tanaka T, Halicka HD, Huang X, Traganos F, Darzynkiewicz Z | year = 2006 | title = Constitutive histone H2AX phosphorylation and ATM activation, the reporters of DNA damage by endogenous oxidants | journal = Cell Cycle | volume = 5 | issue = 17| pages = 1940–5 | pmid = 16940754 | doi = 10.4161/cc.5.17.3191 | pmc = 3488278 }}</ref>
===In chromatin remodeling===
The packaging of eukaryotic DNA into [[chromatin]] presents a barrier to all DNA-based processes that require recruitment of enzymes to their sites of action.  To allow DNA repair, the chromatin must be [[chromatin remodeling|remodeled]].
γH2AX, the phosphorylated form of H2AX, is involved in the steps leading to chromatin decondensation after DNA double-strand breaks.  γH2AX does not, itself, cause chromatin decondensation, but within 30 seconds of [[ionizing radiation]], [[RNF8]] protein can be detected in association with γH2AX.<ref name="pmid18001824">{{cite journal |vauthors=Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, Lukas J |title=RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins |journal=Cell |volume=131 |issue=5 |pages=887–900 |year=2007 |pmid=18001824 |doi=10.1016/j.cell.2007.09.040 |s2cid=14232192 |doi-access=free }}</ref>  RNF8 mediates extensive chromatin decondensation, through its subsequent interaction with [[CHD4]],<ref name="pmid22531782">{{cite journal |vauthors=Luijsterburg MS, Acs K, Ackermann L, Wiegant WW, Bekker-Jensen S, Larsen DH, Khanna KK, van Attikum H, Mailand N, Dantuma NP |title=A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-order chromatin structure |journal=EMBO J. |volume=31 |issue=11 |pages=2511–27 |year=2012 |pmid=22531782 |pmc=3365417 |doi=10.1038/emboj.2012.104 }}</ref> a component of the nucleosome remodeling and deacetylase complex [[Mi-2/NuRD complex|NuRD]].
==γH2AX as an assay for double-strand breaks==
An assay for γH2AX generally reflects the presence of double-strand breaks in DNA, though the assay may indicate other minor phenomena as well.<ref name=Rothkamm>{{cite journal |vauthors=Rothkamm K, Barnard S, Moquet J, Ellender M, Rana Z, Burdak-Rothkamm S |title=DNA damage foci: Meaning and significance |journal=Environ. Mol. Mutagen. |volume=56 |issue=6 |pages=491–504 |year=2015 |pmid=25773265 |doi=10.1002/em.21944 |s2cid=32371215|doi-access=free |bibcode=2015EnvMM..56..491R }}</ref>  On the one hand, overwhelming evidence supports a strong, quantitative correlation between γH2AX foci formation and DNA double-strand break induction following [[ionizing radiation]] exposure, based on absolute yields and distributions induced per unit dose.<ref name=Rothkamm />  On the other hand, not only the formation of distinct γH2AX foci but also the induction of pan-nuclear γH2AX signals have been reported as a cellular reaction to various stressors other than ionizing radiation.<ref name=Meyer>{{cite journal |vauthors=Meyer B, Voss KO, Tobias F, Jakob B, Durante M, Taucher-Scholz G |title=Clustered DNA damage induces pan-nuclear H2AX phosphorylation mediated by ATM and DNA-PK |journal=Nucleic Acids Res. |volume=41 |issue=12 |pages=6109–18 |year=2013 |pmid=23620287 |pmc=3695524 |doi=10.1093/nar/gkt304}}</ref> The γH2AX signal is always stronger at DNA double-strand breaks than in undamaged chromatin.<ref name=Meyer/> γH2AX in undamaged chromatin is thought to possibly be generated via direct phosphorylation of H2AX by activated kinases, most likely diffusing from DNA damage sites. In using γH2AX as a marker for double strand breaks, it is important to recognize that it is a down-stream proxy that can be useful for representing DNA damage repair. It does not represent double strand breaks themselves and this needs careful consideration when interpreting data from such assays.<ref>{{cite journal |last1=Atkinson |first1=Jake |last2=Bezak |first2=Eva |last3=Kempson |first3=Ivan |title=Imaging DNA double-strand breaks — are we there yet? |journal=Nature Reviews Molecular Cell Biology |date=4 July 2022 |volume=23 |issue=9 |pages=579–580 |doi=10.1038/s41580-022-00513-7|pmid=35789205 |s2cid=250283224 }}</ref>
The γH2AX-assay has several disadvantages, therefore new assays have been created. <ref name="pmid30799523 ">{{cite journal |vauthors= Ruprecht N, Hungerbühler MN, Böhm IB, Heverhagen JT |title=Improved identification of DNA double strand breaks: γ-H2AX-epitope visualization by confocal microscopy and 3D reconstructed images. |journal=Radiat Environ Biophys |volume= 58 |issue=2 |pages=295–302 |year=2019 |pmid=30799523  |doi=10.1007/s00411-019-00778-1|doi-access=free |bibcode=2019REBio..58..295R }}</ref>
== Interactions ==
H2AX has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[BARD1]],<ref name = pmid12485996/><ref name = pmid11927591/>
* [[BRCA1]]<ref name = pmid12485996>{{cite journal | vauthors = Mallery DL, Vandenberg CJ, Hiom K | title = Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains | journal = The EMBO Journal | volume = 21 | issue = 24 | pages = 6755–62 | date = Dec 2002 | pmid = 12485996 | pmc = 139111 | doi =  10.1093/emboj/cdf691}}</ref><ref name = pmid11927591>{{cite journal | vauthors = Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ | title = Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase | journal = The Journal of Biological Chemistry | volume = 277 | issue = 24 | pages = 22085–92 | date = Jun 2002 | pmid = 11927591 | doi = 10.1074/jbc.M201252200 | doi-access = free }}</ref><ref name = pmid10959836>{{cite journal | vauthors = Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM | title = A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage | journal = Current Biology | volume = 10 | issue = 15 | pages = 886–95 | pmid = 10959836 | doi =  10.1016/s0960-9822(00)00610-2| year = 2000 | s2cid = 16108315 | doi-access = free | bibcode = 2000CBio...10..886P }}</ref>
* [[Bloom syndrome protein]],<ref name = pmid15364958/>
* [[MDC1]],<ref name = pmid12607005>{{cite journal | vauthors = Stewart GS, Wang B, Bignell CR, Taylor AM, Elledge SJ | title = MDC1 is a mediator of the mammalian DNA damage checkpoint | journal = Nature | volume = 421 | issue = 6926 | pages = 961–6 | date = Feb 2003 | pmid = 12607005 | doi = 10.1038/nature01446 | bibcode = 2003Natur.421..961S | s2cid = 4410773 }}</ref><ref name = pmid14519663>{{cite journal | vauthors = Xu X, Stern DF | title = NFBD1/MDC1 regulates ionizing radiation-induced focus formation by DNA checkpoint signaling and repair factors | journal = FASEB Journal | volume = 17 | issue = 13 | pages = 1842–8 | date = Oct 2003 | pmid = 14519663 | doi = 10.1096/fj.03-0310com | doi-access = free | s2cid = 24870579 }}</ref>
* [[Nibrin]],<ref name = pmid12419185>{{cite journal | vauthors = Kobayashi J, Tauchi H, Sakamoto S, Nakamura A, Morishima K, Matsuura S, Kobayashi T, Tamai K, Tanimoto K, Komatsu K | title = NBS1 localizes to γH2AX foci through interaction with the FHA/BRCT domain | journal = Current Biology | volume = 12 | issue = 21 | pages = 1846–51 | date = Oct 2002 | pmid = 12419185 | doi =  10.1016/s0960-9822(02)01259-9| s2cid = 10686827 | doi-access = free | bibcode = 2002CBio...12.1846K }}</ref>  and
* [[TP53BP1]].<ref name = pmid15364958>{{cite journal | vauthors = Sengupta S, Robles AI, Linke SP, Sinogeeva NI, Zhang R, Pedeux R, Ward IM, Celeste A, Nussenzweig A, Chen J, Halazonetis TD, Harris CC | title = Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest | journal = The Journal of Cell Biology | volume = 166 | issue = 6 | pages = 801–13 | date = Sep 2004 | pmid = 15364958 | pmc = 2172115 | doi = 10.1083/jcb.200405128 }}</ref><ref name = pmid12447390>{{cite journal | vauthors = Fernandez-Capetillo O, Chen HT, Celeste A, Ward I, Romanienko PJ, Morales JC, Naka K, Xia Z, Camerini-Otero RD, Motoyama N, Carpenter PB, Bonner WM, Chen J, Nussenzweig A | title = DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1 | journal = Nature Cell Biology | volume = 4 | issue = 12 | pages = 993–7 | date = Dec 2002 | pmid = 12447390 | doi = 10.1038/ncb884 | s2cid = 12380387 }}</ref><ref name = pmid12697768>{{cite journal | vauthors = Ward IM, Minn K, Jorda KG, Chen J | title = Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX | journal = The Journal of Biological Chemistry | volume = 278 | issue = 22 | pages = 19579–82 | date = May 2003 | pmid = 12697768 | doi = 10.1074/jbc.C300117200 | doi-access = free }}</ref>
{{Div col end}}
== References ==
{{reflist}}
== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Redon C, Pilch D, Rogakou E, Sedelnikova O, Newrock K, Bonner W | title = Histone H2A variants H2AX and H2AZ | journal = Current Opinion in Genetics & Development | volume = 12 | issue = 2 | pages = 162–9 | date = Apr 2002 | pmid = 11893489 | doi = 10.1016/S0959-437X(02)00282-4 }}
* {{cite journal | vauthors = Fernandez-Capetillo O, Lee A, Nussenzweig M, Nussenzweig A | title = H2AX: the histone guardian of the genome | journal = DNA Repair | volume = 3 | issue = 8–9 | pages = 959–67 | year = 2005 | pmid = 15279782 | doi = 10.1016/j.dnarep.2004.03.024 | url = https://zenodo.org/record/1258895 }}
* {{cite journal | vauthors = Mannironi C, Bonner WM, Hatch CL | title = H2A.X. a histone isoprotein with a conserved C-terminal sequence, is encoded by a novel mRNA with both DNA replication type and polyA 3' processing signals | journal = Nucleic Acids Research | volume = 17 | issue = 22 | pages = 9113–26 | date = Nov 1989 | pmid = 2587254 | pmc = 335118 | doi = 10.1093/nar/17.22.9113 }}
* {{cite journal | vauthors = Banerjee S, Smallwood A, Hultén M | title = ATP-dependent reorganization of human sperm nuclear chromatin | journal = Journal of Cell Science | volume = 108 | issue = 2 | pages = 755–65 | date = Feb 1995 | doi = 10.1242/jcs.108.2.755 | pmid = 7769017 }}
* {{cite journal | vauthors = Ivanova VS, Hatch CL, Bonner WM | title = Characterization of the human histone H2A.X gene. Comparison of its promoter with other H2A gene promoters | journal = The Journal of Biological Chemistry | volume = 269 | issue = 39 | pages = 24189–94 | date = Sep 1994 | doi = 10.1016/S0021-9258(19)51067-5 | pmid = 7929075 | doi-access = free }}
* {{cite journal | vauthors = Ivanova VS, Zimonjic D, Popescu N, Bonner WM | title = Chromosomal localization of the human histone H2A.X gene to 11q23.2-q23.3 by fluorescence in situ hybridization | journal = Human Genetics | volume = 94 | issue = 3 | pages = 303–6 | date = Sep 1994 | pmid = 8076949 | doi = 10.1007/BF00208289 | s2cid = 21293682 }}
* {{cite journal | vauthors = Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM | title = DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 10 | pages = 5858–68 | date = Mar 1998 | pmid = 9488723 | doi = 10.1074/jbc.273.10.5858 | doi-access = free }}
* {{cite journal | vauthors = El Kharroubi A, Piras G, Zensen R, Martin MA | title = Transcriptional activation of the integrated chromatin-associated human immunodeficiency virus type 1 promoter | journal = Molecular and Cellular Biology | volume = 18 | issue = 5 | pages = 2535–44 | date = May 1998 | pmid = 9566873 | pmc = 110633 | doi =  10.1128/mcb.18.5.2535}}
* {{cite journal | vauthors = Rogakou EP, Boon C, Redon C, Bonner WM | title = Megabase chromatin domains involved in DNA double-strand breaks in vivo | journal = The Journal of Cell Biology | volume = 146 | issue = 5 | pages = 905–16 | date = Sep 1999 | pmid = 10477747 | pmc = 2169482 | doi = 10.1083/jcb.146.5.905 }}
* {{cite journal | vauthors = Rogakou EP, Nieves-Neira W, Boon C, Pommier Y, Bonner WM | title = Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139 | journal = The Journal of Biological Chemistry | volume = 275 | issue = 13 | pages = 9390–5 | date = Mar 2000 | pmid = 10734083 | doi = 10.1074/jbc.275.13.9390 | doi-access = free }}
* {{cite journal | vauthors = Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM | title = A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage | journal = Current Biology | volume = 10 | issue = 15 | pages = 886–95 | year = 2001 | pmid = 10959836 | doi = 10.1016/S0960-9822(00)00610-2 | s2cid = 16108315 | doi-access = free | bibcode = 2000CBio...10..886P }}
* {{cite journal | vauthors = Deng L, de la Fuente C, Fu P, Wang L, Donnelly R, Wade JD, Lambert P, Li H, Lee CG, Kashanchi F | title = Acetylation of HIV-1 Tat by CBP/P300 increases transcription of integrated HIV-1 genome and enhances binding to core histones | journal = Virology | volume = 277 | issue = 2 | pages = 278–95 | date = Nov 2000 | pmid = 11080476 | doi = 10.1006/viro.2000.0593 | doi-access = free }}
* {{cite journal | vauthors = Chen HT, Bhandoola A, Difilippantonio MJ, Zhu J, Brown MJ, Tai X, Rogakou EP, Brotz TM, Bonner WM, Ried T, Nussenzweig A | title = Response to RAG-mediated VDJ cleavage by NBS1 and γH2AX | journal = Science | volume = 290 | issue = 5498 | pages = 1962–5 | date = Dec 2000 | pmid = 11110662 | pmc = 4721589 | doi = 10.1126/science.290.5498.1962 | bibcode = 2000Sci...290.1962C }}
* {{cite journal | vauthors = Chadwick BP, Willard HF | title = Histone H2A variants and the inactive X chromosome: identification of a second macroH2A variant | journal = Human Molecular Genetics | volume = 10 | issue = 10 | pages = 1101–13 | date = May 2001 | pmid = 11331621 | doi = 10.1093/hmg/10.10.1101 | doi-access = free }}
* {{cite journal | vauthors = Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ | title = ATM phosphorylates histone H2AX in response to DNA double-strand breaks | journal = The Journal of Biological Chemistry | volume = 276 | issue = 45 | pages = 42462–7 | date = Nov 2001 | pmid = 11571274 | doi = 10.1074/jbc.C100466200 | url = https://digital.library.unt.edu/ark:/67531/metadc742264/ | doi-access = free }}
* {{cite journal | vauthors = Ward IM, Chen J | title = Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress | journal = The Journal of Biological Chemistry | volume = 276 | issue = 51 | pages = 47759–62 | date = Dec 2001 | pmid = 11673449 | doi = 10.1074/jbc.C100569200 | doi-access = free }}
* {{cite journal | vauthors = Deng L, Wang D, de la Fuente C, Wang L, Li H, Lee CG, Donnelly R, Wade JD, Lambert P, Kashanchi F | title = Enhancement of the p300 HAT activity by HIV-1 Tat on chromatin DNA | journal = Virology | volume = 289 | issue = 2 | pages = 312–26 | date = Oct 2001 | pmid = 11689053 | doi = 10.1006/viro.2001.1129 | doi-access = free }}
* {{cite journal | vauthors = Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ | title = Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase | journal = The Journal of Biological Chemistry | volume = 277 | issue = 24 | pages = 22085–92 | date = Jun 2002 | pmid = 11927591 | doi = 10.1074/jbc.M201252200 | doi-access = free }}
* {{cite journal | vauthors = Zhu H, Hunter TC, Pan S, Yau PM, Bradbury EM, Chen X | title = Residue-specific mass signatures for the efficient detection of protein modifications by mass spectrometry | journal = Analytical Chemistry | volume = 74 | issue = 7 | pages = 1687–94 | date = Apr 2002 | pmid = 12033261 | doi = 10.1021/ac010853p | s2cid = 26392831 }}
{{refend}}
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[[Category:DNA repair]]