XRCC2: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''DNA repair protein XRCC2''' is a [[protein]] that in humans is encoded by the ''XRCC2'' [[gene]].<ref name="pmid7607692">{{cite journal | vauthors = Jones NJ, Zhao Y, Siciliano MJ, Thompson LH | title = Assignment of the XRCC2 human DNA repair gene to chromosome 7q36 by complementation analysis | journal = Genomics | volume = 26 | issue = 3 | pages = 619–22 | date = Apr 1995 | pmid = 7607692 | pmc =  | doi = 10.1016/0888-7543(95)80187-Q }}</ref><ref name="pmid10422536">{{cite journal | vauthors = Cui X, Brenneman M, Meyne J, Oshimura M, Goodwin EH, Chen DJ | title = The XRCC2 and XRCC3 repair genes are required for chromosome stability in mammalian cells | journal = Mutation Research | volume = 434 | issue = 2 | pages = 75–88 | date = Jun 1999 | pmid = 10422536 | pmc =  | doi = 10.1016/s0921-8777(99)00010-5 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: XRCC2 X-ray repair complementing defective repair in Chinese hamster cells 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7516| accessdate = }}</ref>
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| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = X-ray repair complementing defective repair in Chinese hamster cells 2
| HGNCid = 12829
| Symbol = XRCC2
| AltSymbols =; DKFZp781P0919
| OMIM = 600375
| ECnumber = 
| Homologene = 3964
| MGIid = 1927345
| GeneAtlas_image1 = PBB_GE_XRCC2_207598_x_at_tn.png
| Function = {{GNF_GO|id=GO:0003677 |text = DNA binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0008094 |text = DNA-dependent ATPase activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006281 |text = DNA repair}} {{GNF_GO|id=GO:0006310 |text = DNA recombination}} {{GNF_GO|id=GO:0007126 |text = meiosis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7516
    | Hs_Ensembl = ENSG00000196584
    | Hs_RefseqProtein = NP_005422
    | Hs_RefseqmRNA = NM_005431
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 7
    | Hs_GenLoc_start = 151974522
    | Hs_GenLoc_end = 152004183
    | Hs_Uniprot = O43543
    | Mm_EntrezGene = 57434
    | Mm_Ensembl = ENSMUSG00000028933
    | Mm_RefseqmRNA = NM_020570
    | Mm_RefseqProtein = NP_065595
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 5
    | Mm_GenLoc_start = 25199877
    | Mm_GenLoc_end = 25215862
    | Mm_Uniprot = Q9CX47
  }}
}}
'''X-ray repair complementing defective repair in Chinese hamster cells 2''', also known as '''XRCC2''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: XRCC2 X-ray repair complementing defective repair in Chinese hamster cells 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7516| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene is involved in the repair of DNA double-strand breaks by homologous recombination and it functionally complements Chinese hamster irs1, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents.<ref name="entrez"/>
{{PBB_Summary
| section_title =
| summary_text = This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene is involved in the repair of DNA double-strand breaks by homologous recombination and it functionally complements Chinese hamster irs1, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents.<ref name="entrez">{{cite web | title = Entrez Gene: XRCC2 X-ray repair complementing defective repair in Chinese hamster cells 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7516| accessdate = }}</ref>
}}


==References==
The XRCC2 protein is one of five human [[Homology (biology)#Paralogy|paralogs]] of [[RAD51]], including RAD51B ([[RAD51L1]]), RAD51C (RAD51L2), RAD51D ([[RAD51L3]]), XRCC2 and [[XRCC3]].  They each share about 25% amino acid sequence identity with RAD51 and each other.<ref name="pmid14704354">{{cite journal |vauthors=Miller KA, Sawicka D, Barsky D, Albala JS |title=Domain mapping of the Rad51 paralog protein complexes |journal=Nucleic Acids Res. |volume=32 |issue=1 |pages=169–78 |year=2004 |pmid=14704354 |pmc=373258 |doi=10.1093/nar/gkg925 |url=}}</ref>
{{reflist|2}}
 
==Further reading==
The RAD51 paralogs are all required for efficient DNA double-strand break repair by [[homologous recombination]] and depletion of any paralog results in significant decreases in homologous recombination frequency.<ref name=Chun>{{cite journal |vauthors=Chun J, Buechelmaier ES, Powell SN |title=Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway |journal=Mol. Cell. Biol. |volume=33 |issue=2 |pages=387–95 |year=2013 |pmid=23149936 |pmc=3554112 |doi=10.1128/MCB.00465-12 |url=}}</ref>
 
XRCC2 forms a four-part complex with three related paralogs: BCDX2 (RAD51B-RAD51C-RAD51D-XRCC2) while two paralogs form a second complex CX3 (RAD51C-XRCC3). These two complexes act at two different stages of [[homologous recombination]]al [[DNA repair]].  The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites.<ref name=Chun />  The BCDX2 complex appears to act by facilitating the assembly or stability of the [[RAD51#Function|RAD51 nucleoprotein filament]].
 
The CX3 complex acts downstream of RAD51 recruitment to damage sites.<ref name=Chun />  The CX3 complex was shown to associate with [[Holliday junction]] resolvase activity, probably in a role of stabilizing [[gene conversion]] tracts.<ref name=Chun />
 
== Interactions ==
 
XRCC2 has been shown to [[Protein-protein interaction|interact]] with [[RAD51L3]],<ref name=pmid10749867>{{cite journal | vauthors = Schild D, Lio YC, Collins DW, Tsomondo T, Chen DJ | title = Evidence for simultaneous protein interactions between human Rad51 paralogs | journal = The Journal of Biological Chemistry | volume = 275 | issue = 22 | pages = 16443–9 | date = Jun 2000 | pmid = 10749867 | doi = 10.1074/jbc.M001473200 }}</ref><ref name=pmid12975363>{{cite journal | vauthors = Braybrooke JP, Li JL, Wu L, Caple F, Benson FE, Hickson ID | title = Functional interaction between the Bloom's syndrome helicase and the RAD51 paralog, RAD51L3 (RAD51D) | journal = The Journal of Biological Chemistry | volume = 278 | issue = 48 | pages = 48357–66 | date = Nov 2003 | pmid = 12975363 | doi = 10.1074/jbc.M308838200 }}</ref><ref name=pmid15115758>{{cite journal | vauthors = Hussain S, Wilson JB, Medhurst AL, Hejna J, Witt E, Ananth S, Davies A, Masson JY, Moses R, West SC, de Winter JP, Ashworth A, Jones NJ, Mathew CG | title = Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways | journal = Human Molecular Genetics | volume = 13 | issue = 12 | pages = 1241–8 | date = Jun 2004 | pmid = 15115758 | doi = 10.1093/hmg/ddh135 }}</ref><ref name=pmid11842113>{{cite journal | vauthors = Liu N, Schild D, Thelen MP, Thompson LH | title = Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs in human cells | journal = Nucleic Acids Research | volume = 30 | issue = 4 | pages = 1009–15 | date = Feb 2002 | pmid = 11842113 | pmc = 100342 | doi = 10.1093/nar/30.4.1009 }}</ref> [[Bloom syndrome protein]]<ref name=pmid12975363/> and [[RAD51C]].<ref name=pmid11842113/><ref name=pmid11744692>{{cite journal | vauthors = Miller KA, Yoshikawa DM, McConnell IR, Clark R, Schild D, Albala JS | title = RAD51C interacts with RAD51B and is central to a larger protein complex in vivo exclusive of RAD51 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 10 | pages = 8406–11 | date = Mar 2002 | pmid = 11744692 | doi = 10.1074/jbc.M108306200 }}</ref>
 
==Epigenetic deficiency in cancer==
 
There are two known [[Epigenetics|epigenetic]] causes of XRCC2 deficiency that appear to increase cancer risk.  These are [[DNA methylation|methylation]]  of the ''XRCC2'' promoter and epigenetic repression of ''XRCC2'' by over-expression of [[EZH2]] protein.
 
The ''XRCC2'' gene was found to be hypermethylated in the promoter region in 52 of 54 cases of cervical cancer.<ref name="pmid24485306">{{cite journal |vauthors=Paulíková S, Chmelařová M, Petera J, Palička V, Paulík A |title=Hypermethylation of RAD51L3 and XRCC2 genes to predict late toxicity in chemoradiotherapy-treated cervical cancer patients |journal=Folia Biol. (Praha) |volume=59 |issue=6 |pages=240–5 |year=2013 |pmid=24485306 |doi= |url=}}</ref>  Promoter hypermethylation reduces gene expression, and thus would reduce the tumor suppressing homologous recombinational repair otherwise supported by ''XRCC2''.
 
Increased expression of EZH2 leads to epigenetic repression of RAD51 paralogs, including XRCC2, and thus reduces [[homologous recombination]]al repair.<ref name=Zeidler>{{cite journal |vauthors=Zeidler M, Kleer CG |title=The Polycomb group protein Enhancer of Zeste 2: its links to DNA repair and breast cancer |journal=J. Mol. Histol. |volume=37 |issue=5-7 |pages=219–23 |year=2006 |pmid=16855786 |doi=10.1007/s10735-006-9042-9 |url=}}</ref>  This reduction was proposed to be a cause of breast cancer.<ref name=Zeidler />  EZH2 is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2) which catalyzes methylation of histone H3 at lysine 27 (H3K27me) and mediates gene silencing of target genes via local chromatin reorganization.<ref name="Völkel">{{cite journal |vauthors=Völkel P, Dupret B, Le Bourhis X, Angrand PO |title=Diverse involvement of EZH2 in cancer epigenetics |journal=Am J Transl Res |volume=7 |issue=2 |pages=175–93 |year=2015 |pmid=25901190 |pmc=4399085 |doi= |url=}}</ref>  EZH2 protein is up-regulated in numerous cancers.<ref name="Völkel" /><ref name="pmid22187039">{{cite journal |vauthors=Chang CJ, Hung MC |title=The role of EZH2 in tumour progression |journal=Br. J. Cancer |volume=106 |issue=2 |pages=243–7 |year=2012 |pmid=22187039 |pmc=3261672 |doi=10.1038/bjc.2011.551 |url=}}</ref>  EZH2 mRNA is up-regulated, on average, 7.5-fold in breast cancer, and between 40% to 75% of breast cancers have over-expressed EZH2 protein.<ref name="pmid14500907">{{cite journal |vauthors=Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP, Hayes DF, Sabel MS, Livant D, Weiss SJ, Rubin MA, Chinnaiyan AM |title=EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=100 |issue=20 |pages=11606–11 |year=2003 |pmid=14500907 |pmc=208805 |doi=10.1073/pnas.1933744100 |url=}}</ref>
 
== References ==
{{Reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Thacker J, Tambini CE, Simpson PJ, Tsui LC, Scherer SW | title = Localization to chromosome 7q36.1 of the human XRCC2 gene, determining sensitivity to DNA-damaging agents | journal = Human Molecular Genetics | volume = 4 | issue = 1 | pages = 113–20 | date = Jan 1995 | pmid = 7711722 | doi = 10.1093/hmg/4.1.113 }}
| citations =
* {{cite journal | vauthors = Tambini CE, George AM, Rommens JM, Tsui LC, Scherer SW, Thacker J | title = The XRCC2 DNA repair gene: identification of a positional candidate | journal = Genomics | volume = 41 | issue = 1 | pages = 84–92 | date = Apr 1997 | pmid = 9126486 | doi = 10.1006/geno.1997.4636 }}
*{{cite journal | author=Jones NJ, Zhao Y, Siciliano MJ, Thompson LH |title=Assignment of the XRCC2 human DNA repair gene to chromosome 7q36 by complementation analysis. |journal=Genomics |volume=26 |issue= 3 |pages= 619-22 |year= 1995 |pmid= 7607692 |doi=  }}
* {{cite journal | vauthors = Cartwright R, Tambini CE, Simpson PJ, Thacker J | title = The XRCC2 DNA repair gene from human and mouse encodes a novel member of the recA/RAD51 family | journal = Nucleic Acids Research | volume = 26 | issue = 13 | pages = 3084–9 | date = Jul 1998 | pmid = 9628903 | pmc = 147676 | doi = 10.1093/nar/26.13.3084 }}
*{{cite journal  | author=Thacker J, Tambini CE, Simpson PJ, ''et al.'' |title=Localization to chromosome 7q36.1 of the human XRCC2 gene, determining sensitivity to DNA-damaging agents. |journal=Hum. Mol. Genet. |volume=4 |issue= 1 |pages= 113-20 |year= 1995 |pmid= 7711722 |doi= }}
* {{cite journal | vauthors = Liu N, Lamerdin JE, Tebbs RS, Schild D, Tucker JD, Shen MR, Brookman KW, Siciliano MJ, Walter CA, Fan W, Narayana LS, Zhou ZQ, Adamson AW, Sorensen KJ, Chen DJ, Jones NJ, Thompson LH | title = XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages | journal = Molecular Cell | volume = 1 | issue = 6 | pages = 783–93 | date = May 1998 | pmid = 9660962 | doi = 10.1016/S1097-2765(00)80078-7 }}
*{{cite journal | author=Tambini CE, George AM, Rommens JM, ''et al.'' |title=The XRCC2 DNA repair gene: identification of a positional candidate. |journal=Genomics |volume=41 |issue= 1 |pages= 84-92 |year= 1997 |pmid= 9126486 |doi= 10.1006/geno.1997.4636 }}
* {{cite journal | vauthors = Johnson RD, Liu N, Jasin M | title = Mammalian XRCC2 promotes the repair of DNA double-strand breaks by homologous recombination | journal = Nature | volume = 401 | issue = 6751 | pages = 397–9 | date = Sep 1999 | pmid = 10517641 | doi = 10.1038/43932 }}
*{{cite journal | author=Cartwright R, Tambini CE, Simpson PJ, Thacker J |title=The XRCC2 DNA repair gene from human and mouse encodes a novel member of the recA/RAD51 family. |journal=Nucleic Acids Res. |volume=26 |issue= 13 |pages= 3084-9 |year= 1998 |pmid= 9628903 |doi= }}
* {{cite journal | vauthors = Schild D, Lio YC, Collins DW, Tsomondo T, Chen DJ | title = Evidence for simultaneous protein interactions between human Rad51 paralogs | journal = The Journal of Biological Chemistry | volume = 275 | issue = 22 | pages = 16443–9 | date = Jun 2000 | pmid = 10749867 | doi = 10.1074/jbc.M001473200 }}
*{{cite journal | author=Liu N, Lamerdin JE, Tebbs RS, ''et al.'' |title=XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages. |journal=Mol. Cell |volume=1 |issue= 6 |pages= 783-93 |year= 1998 |pmid= 9660962 |doi= }}
* {{cite journal | vauthors = Braybrooke JP, Spink KG, Thacker J, Hickson ID | title = The RAD51 family member, RAD51L3, is a DNA-stimulated ATPase that forms a complex with XRCC2 | journal = The Journal of Biological Chemistry | volume = 275 | issue = 37 | pages = 29100–6 | date = Sep 2000 | pmid = 10871607 | doi = 10.1074/jbc.M002075200 }}
*{{cite journal  | author=Cui X, Brenneman M, Meyne J, ''et al.'' |title=The XRCC2 and XRCC3 repair genes are required for chromosome stability in mammalian cells. |journal=Mutat. Res. |volume=434 |issue= 2 |pages= 75-88 |year= 1999 |pmid= 10422536 |doi=  }}
* {{cite journal | vauthors = O'Regan P, Wilson C, Townsend S, Thacker J | title = XRCC2 is a nuclear RAD51-like protein required for damage-dependent RAD51 focus formation without the need for ATP binding | journal = The Journal of Biological Chemistry | volume = 276 | issue = 25 | pages = 22148–53 | date = Jun 2001 | pmid = 11301337 | doi = 10.1074/jbc.M102396200 }}
*{{cite journal | author=Johnson RD, Liu N, Jasin M |title=Mammalian XRCC2 promotes the repair of DNA double-strand breaks by homologous recombination. |journal=Nature |volume=401 |issue= 6751 |pages= 397-9 |year= 1999 |pmid= 10517641 |doi= 10.1038/43932 }}
* {{cite journal | vauthors = Miller KA, Yoshikawa DM, McConnell IR, Clark R, Schild D, Albala JS | title = RAD51C interacts with RAD51B and is central to a larger protein complex in vivo exclusive of RAD51 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 10 | pages = 8406–11 | date = Mar 2002 | pmid = 11744692 | doi = 10.1074/jbc.M108306200 }}
*{{cite journal | author=Schild D, Lio YC, Collins DW, ''et al.'' |title=Evidence for simultaneous protein interactions between human Rad51 paralogs. |journal=J. Biol. Chem. |volume=275 |issue= 22 |pages= 16443-9 |year= 2000 |pmid= 10749867 |doi= 10.1074/jbc.M001473200 }}
* {{cite journal | vauthors = Masson JY, Tarsounas MC, Stasiak AZ, Stasiak A, Shah R, McIlwraith MJ, Benson FE, West SC | title = Identification and purification of two distinct complexes containing the five RAD51 paralogs | journal = Genes & Development | volume = 15 | issue = 24 | pages = 3296–307 | date = Dec 2001 | pmid = 11751635 | pmc = 312846 | doi = 10.1101/gad.947001 }}
*{{cite journal | author=Braybrooke JP, Spink KG, Thacker J, Hickson ID |title=The RAD51 family member, RAD51L3, is a DNA-stimulated ATPase that forms a complex with XRCC2. |journal=J. Biol. Chem. |volume=275 |issue= 37 |pages= 29100-6 |year= 2000 |pmid= 10871607 |doi= 10.1074/jbc.M002075200 }}
* {{cite journal | vauthors = Kurumizaka H, Ikawa S, Nakada M, Enomoto R, Kagawa W, Kinebuchi T, Yamazoe M, Yokoyama S, Shibata T | title = Homologous pairing and ring and filament structure formation activities of the human Xrcc2*Rad51D complex | journal = The Journal of Biological Chemistry | volume = 277 | issue = 16 | pages = 14315–20 | date = Apr 2002 | pmid = 11834724 | doi = 10.1074/jbc.M105719200 }}
*{{cite journal | author=O'Regan P, Wilson C, Townsend S, Thacker J |title=XRCC2 is a nuclear RAD51-like protein required for damage-dependent RAD51 focus formation without the need for ATP binding. |journal=J. Biol. Chem. |volume=276 |issue= 25 |pages= 22148-53 |year= 2001 |pmid= 11301337 |doi= 10.1074/jbc.M102396200 }}
* {{cite journal | vauthors = Wiese C, Collins DW, Albala JS, Thompson LH, Kronenberg A, Schild D | title = Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human cells | journal = Nucleic Acids Research | volume = 30 | issue = 4 | pages = 1001–8 | date = Feb 2002 | pmid = 11842112 | pmc = 100332 | doi = 10.1093/nar/30.4.1001 }}
*{{cite journal | author=Miller KA, Yoshikawa DM, McConnell IR, ''et al.'' |title=RAD51C interacts with RAD51B and is central to a larger protein complex in vivo exclusive of RAD51. |journal=J. Biol. Chem. |volume=277 |issue= 10 |pages= 8406-11 |year= 2002 |pmid= 11744692 |doi= 10.1074/jbc.M108306200 }}
* {{cite journal | vauthors = Liu N, Schild D, Thelen MP, Thompson LH | title = Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs in human cells | journal = Nucleic Acids Research | volume = 30 | issue = 4 | pages = 1009–15 | date = Feb 2002 | pmid = 11842113 | pmc = 100342 | doi = 10.1093/nar/30.4.1009 }}
*{{cite journal | author=Masson JY, Tarsounas MC, Stasiak AZ, ''et al.'' |title=Identification and purification of two distinct complexes containing the five RAD51 paralogs. |journal=Genes Dev. |volume=15 |issue= 24 |pages= 3296-307 |year= 2002 |pmid= 11751635 |doi= 10.1101/gad.947001 }}
* {{cite journal | vauthors = Braybrooke JP, Li JL, Wu L, Caple F, Benson FE, Hickson ID | title = Functional interaction between the Bloom's syndrome helicase and the RAD51 paralog, RAD51L3 (RAD51D) | journal = The Journal of Biological Chemistry | volume = 278 | issue = 48 | pages = 48357–66 | date = Nov 2003 | pmid = 12975363 | doi = 10.1074/jbc.M308838200 }}
*{{cite journal | author=Kurumizaka H, Ikawa S, Nakada M, ''et al.'' |title=Homologous pairing and ring and filament structure formation activities of the human Xrcc2*Rad51D complex. |journal=J. Biol. Chem. |volume=277 |issue= 16 |pages= 14315-20 |year= 2002 |pmid= 11834724 |doi= 10.1074/jbc.M105719200 }}
* {{cite journal | vauthors = Mohindra A, Bolderson E, Stone J, Wells M, Helleday T, Meuth M | title = A tumour-derived mutant allele of XRCC2 preferentially suppresses homologous recombination at DNA replication forks | journal = Human Molecular Genetics | volume = 13 | issue = 2 | pages = 203–12 | date = Jan 2004 | pmid = 14645207 | doi = 10.1093/hmg/ddh022 }}
*{{cite journal | author=Wiese C, Collins DW, Albala JS, ''et al.'' |title=Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human cells. |journal=Nucleic Acids Res. |volume=30 |issue= 4 |pages= 1001-8 |year= 2002 |pmid= 11842112 |doi= }}
* {{cite journal | vauthors = Tarsounas M, Davies AA, West SC | title = RAD51 localization and activation following DNA damage | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 359 | issue = 1441 | pages = 87–93 | date = Jan 2004 | pmid = 15065660 | pmc = 1693300 | doi = 10.1098/rstb.2003.1368 }}
*{{cite journal | author=Liu N, Schild D, Thelen MP, Thompson LH |title=Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs in human cells. |journal=Nucleic Acids Res. |volume=30 |issue= 4 |pages= 1009-15 |year= 2002 |pmid= 11842113 |doi=  }}
* {{cite journal | vauthors = Hussain S, Wilson JB, Medhurst AL, Hejna J, Witt E, Ananth S, Davies A, Masson JY, Moses R, West SC, de Winter JP, Ashworth A, Jones NJ, Mathew CG | title = Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways | journal = Human Molecular Genetics | volume = 13 | issue = 12 | pages = 1241–8 | date = Jun 2004 | pmid = 15115758 | doi = 10.1093/hmg/ddh135 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal | author=Braybrooke JP, Li JL, Wu L, ''et al.'' |title=Functional interaction between the Bloom's syndrome helicase and the RAD51 paralog, RAD51L3 (RAD51D). |journal=J. Biol. Chem. |volume=278 |issue= 48 |pages= 48357-66 |year= 2004 |pmid= 12975363 |doi= 10.1074/jbc.M308838200 }}
*{{cite journal | author=Mohindra A, Bolderson E, Stone J, ''et al.'' |title=A tumour-derived mutant allele of XRCC2 preferentially suppresses homologous recombination at DNA replication forks. |journal=Hum. Mol. Genet. |volume=13 |issue= 2 |pages= 203-12 |year= 2004 |pmid= 14645207 |doi= 10.1093/hmg/ddh022 }}
*{{cite journal | author=Tarsounas M, Davies AA, West SC |title=RAD51 localization and activation following DNA damage. |journal=Philos. Trans. R. Soc. Lond., B, Biol. Sci. |volume=359 |issue= 1441 |pages= 87-93 |year= 2004 |pmid= 15065660 |doi= 10.1098/rstb.2003.1368 }}
*{{cite journal | author=Hussain S, Wilson JB, Medhurst AL, ''et al.'' |title=Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways. |journal=Hum. Mol. Genet. |volume=13 |issue= 12 |pages= 1241-8 |year= 2004 |pmid= 15115758 |doi= 10.1093/hmg/ddh135 }}
}}
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Latest revision as of 21:43, 18 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
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DNA repair protein XRCC2 is a protein that in humans is encoded by the XRCC2 gene.[1][2][3]

Function

This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene is involved in the repair of DNA double-strand breaks by homologous recombination and it functionally complements Chinese hamster irs1, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents.[3]

The XRCC2 protein is one of five human paralogs of RAD51, including RAD51B (RAD51L1), RAD51C (RAD51L2), RAD51D (RAD51L3), XRCC2 and XRCC3. They each share about 25% amino acid sequence identity with RAD51 and each other.[4]

The RAD51 paralogs are all required for efficient DNA double-strand break repair by homologous recombination and depletion of any paralog results in significant decreases in homologous recombination frequency.[5]

XRCC2 forms a four-part complex with three related paralogs: BCDX2 (RAD51B-RAD51C-RAD51D-XRCC2) while two paralogs form a second complex CX3 (RAD51C-XRCC3). These two complexes act at two different stages of homologous recombinational DNA repair. The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites.[5] The BCDX2 complex appears to act by facilitating the assembly or stability of the RAD51 nucleoprotein filament.

The CX3 complex acts downstream of RAD51 recruitment to damage sites.[5] The CX3 complex was shown to associate with Holliday junction resolvase activity, probably in a role of stabilizing gene conversion tracts.[5]

Interactions

XRCC2 has been shown to interact with RAD51L3,[6][7][8][9] Bloom syndrome protein[7] and RAD51C.[9][10]

Epigenetic deficiency in cancer

There are two known epigenetic causes of XRCC2 deficiency that appear to increase cancer risk. These are methylation of the XRCC2 promoter and epigenetic repression of XRCC2 by over-expression of EZH2 protein.

The XRCC2 gene was found to be hypermethylated in the promoter region in 52 of 54 cases of cervical cancer.[11] Promoter hypermethylation reduces gene expression, and thus would reduce the tumor suppressing homologous recombinational repair otherwise supported by XRCC2.

Increased expression of EZH2 leads to epigenetic repression of RAD51 paralogs, including XRCC2, and thus reduces homologous recombinational repair.[12] This reduction was proposed to be a cause of breast cancer.[12] EZH2 is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2) which catalyzes methylation of histone H3 at lysine 27 (H3K27me) and mediates gene silencing of target genes via local chromatin reorganization.[13] EZH2 protein is up-regulated in numerous cancers.[13][14] EZH2 mRNA is up-regulated, on average, 7.5-fold in breast cancer, and between 40% to 75% of breast cancers have over-expressed EZH2 protein.[15]

References

  1. ↑ Jones NJ, Zhao Y, Siciliano MJ, Thompson LH (Apr 1995). "Assignment of the XRCC2 human DNA repair gene to chromosome 7q36 by complementation analysis". Genomics. 26 (3): 619–22. doi:10.1016/0888-7543(95)80187-Q. PMID 7607692.
  2. ↑ Cui X, Brenneman M, Meyne J, Oshimura M, Goodwin EH, Chen DJ (Jun 1999). "The XRCC2 and XRCC3 repair genes are required for chromosome stability in mammalian cells". Mutation Research. 434 (2): 75–88. doi:10.1016/s0921-8777(99)00010-5. PMID 10422536.
  3. ↑ 3.0 3.1 "Entrez Gene: XRCC2 X-ray repair complementing defective repair in Chinese hamster cells 2".
  4. ↑ Miller KA, Sawicka D, Barsky D, Albala JS (2004). "Domain mapping of the Rad51 paralog protein complexes". Nucleic Acids Res. 32 (1): 169–78. doi:10.1093/nar/gkg925. PMC 373258. PMID 14704354.
  5. ↑ 5.0 5.1 5.2 5.3 Chun J, Buechelmaier ES, Powell SN (2013). "Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway". Mol. Cell. Biol. 33 (2): 387–95. doi:10.1128/MCB.00465-12. PMC 3554112. PMID 23149936.
  6. ↑ Schild D, Lio YC, Collins DW, Tsomondo T, Chen DJ (Jun 2000). "Evidence for simultaneous protein interactions between human Rad51 paralogs". The Journal of Biological Chemistry. 275 (22): 16443–9. doi:10.1074/jbc.M001473200. PMID 10749867.
  7. ↑ 7.0 7.1 Braybrooke JP, Li JL, Wu L, Caple F, Benson FE, Hickson ID (Nov 2003). "Functional interaction between the Bloom's syndrome helicase and the RAD51 paralog, RAD51L3 (RAD51D)". The Journal of Biological Chemistry. 278 (48): 48357–66. doi:10.1074/jbc.M308838200. PMID 12975363.
  8. ↑ Hussain S, Wilson JB, Medhurst AL, Hejna J, Witt E, Ananth S, Davies A, Masson JY, Moses R, West SC, de Winter JP, Ashworth A, Jones NJ, Mathew CG (Jun 2004). "Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways". Human Molecular Genetics. 13 (12): 1241–8. doi:10.1093/hmg/ddh135. PMID 15115758.
  9. ↑ 9.0 9.1 Liu N, Schild D, Thelen MP, Thompson LH (Feb 2002). "Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs in human cells". Nucleic Acids Research. 30 (4): 1009–15. doi:10.1093/nar/30.4.1009. PMC 100342. PMID 11842113.
  10. ↑ Miller KA, Yoshikawa DM, McConnell IR, Clark R, Schild D, Albala JS (Mar 2002). "RAD51C interacts with RAD51B and is central to a larger protein complex in vivo exclusive of RAD51". The Journal of Biological Chemistry. 277 (10): 8406–11. doi:10.1074/jbc.M108306200. PMID 11744692.
  11. ↑ Paulíková S, Chmelařová M, Petera J, Palička V, Paulík A (2013). "Hypermethylation of RAD51L3 and XRCC2 genes to predict late toxicity in chemoradiotherapy-treated cervical cancer patients". Folia Biol. (Praha). 59 (6): 240–5. PMID 24485306.
  12. ↑ 12.0 12.1 Zeidler M, Kleer CG (2006). "The Polycomb group protein Enhancer of Zeste 2: its links to DNA repair and breast cancer". J. Mol. Histol. 37 (5–7): 219–23. doi:10.1007/s10735-006-9042-9. PMID 16855786.
  13. ↑ 13.0 13.1 Völkel P, Dupret B, Le Bourhis X, Angrand PO (2015). "Diverse involvement of EZH2 in cancer epigenetics". Am J Transl Res. 7 (2): 175–93. PMC 4399085. PMID 25901190.
  14. ↑ Chang CJ, Hung MC (2012). "The role of EZH2 in tumour progression". Br. J. Cancer. 106 (2): 243–7. doi:10.1038/bjc.2011.551. PMC 3261672. PMID 22187039.
  15. ↑ Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP, Hayes DF, Sabel MS, Livant D, Weiss SJ, Rubin MA, Chinnaiyan AM (2003). "EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells". Proc. Natl. Acad. Sci. U.S.A. 100 (20): 11606–11. doi:10.1073/pnas.1933744100. PMC 208805. PMID 14500907.

Further reading

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