| Structural highlights
Disease
XRCC3_HUMAN Disease susceptibility is associated with variants affecting the gene represented in this entry. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Variant p.Thr341Met has been reported to be associated with an increased risk for CMM6 (PubMed:11059748). Further studies have shown that this variant is functional in homology-directed DNA repair, and the association of XRCC3 with CMM6 has not been confirmed (PubMed:12037675, PubMed:12376526, PubMed:26137085, PubMed:26922354).[1] [2] [3] [4] [5]
Function
XRCC3_HUMAN Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions. Part of the RAD51 paralog protein complex CX3 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, CX3 acts downstream of RAD51 recruitment; the complex binds predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junctions of replication forks. Involved in HJ resolution and thus in processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex and seems to involve GEN1 during mitotic cell cycle progression. Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and RAD51C.[6] [7] [8] [9]
References
- ↑ Winsey SL, Haldar NA, Marsh HP, Bunce M, Marshall SE, Harris AL, Wojnarowska F, Welsh KI. A variant within the DNA repair gene XRCC3 is associated with the development of melanoma skin cancer. Cancer Res. 2000 Oct 15;60(20):5612-6 PMID:11059748
- ↑ Araujo FD, Pierce AJ, Stark JM, Jasin M. Variant XRCC3 implicated in cancer is functional in homology-directed repair of double-strand breaks. Oncogene. 2002 Jun 13;21(26):4176-80. PMID:12037675 doi:10.1038/sj.onc.1205539
- ↑ Duan Z, Shen H, Lee JE, Gershenwald JE, Ross MI, Mansfield PF, Duvic M, Strom SS, Spitz MR, Wei Q. DNA repair gene XRCC3 241Met variant is not associated with risk of cutaneous malignant melanoma. Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):1142-3 PMID:12376526
- ↑ Fan J, Fan Y, Kang X, Zhao L. XRCC3 T241M polymorphism and melanoma skin cancer risk: A meta-analysis. Oncol Lett. 2015 May;9(5):2425-2429. PMID:26137085 doi:10.3892/ol.2015.3040
- ↑ Zeng Y, Ma F, Gao W, Wang Y, Liu C. Quantitative assessment of the influence of X-ray repair cross-complementing group 3 rs861539 polymorphism and cutaneous melanoma susceptibility. Arch Dermatol Res. 2016 Apr;308(3):173-81. PMID:26922354 doi:10.1007/s00403-016-1629-8
- ↑ Liu Y, Masson JY, Shah R, O'Regan P, West SC. RAD51C is required for Holliday junction processing in mammalian cells. Science. 2004 Jan 9;303(5655):243-6. PMID:14716019 doi:10.1126/science.1093037
- ↑ Sage JM, Gildemeister OS, Knight KL. Discovery of a novel function for human Rad51: maintenance of the mitochondrial genome. J Biol Chem. 2010 Jun 18;285(25):18984-90. doi: 10.1074/jbc.M109.099846. Epub, 2010 Apr 22. PMID:20413593 doi:10.1074/jbc.M109.099846
- ↑ Rodrigue A, Coulombe Y, Jacquet K, Gagné JP, Roques C, Gobeil S, Poirier G, Masson JY. The RAD51 paralogs ensure cellular protection against mitotic defects and aneuploidy. J Cell Sci. 2013 Jan 1;126(Pt 1):348-59. PMID:23108668 doi:10.1242/jcs.114595
- ↑ Chun J, Buechelmaier ES, Powell SN. Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway. Mol Cell Biol. 2013 Jan;33(2):387-95. PMID:23149936 doi:10.1128/MCB.00465-12
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