8gbj

Structural highlights

Disease

RA51C_HUMAN Fanconi anemia;Hereditary breast and ovarian cancer syndrome. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

RA51C_HUMAN Essential for the homologous recombination (HR) pathway of DNA repair. Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Part of the RAD51 paralog protein complexes BCDX2 and CX3 which act at different stages of the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 seems to act downstream of BRCA2 recruitment and upstream of RAD51 recruitment; CX3 seems to act downstream of RAD51 recruitment; both complexes bind predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. The BCDX2 subcomplex RAD51B:RAD51C exhibits single-stranded DNA-dependent ATPase activity suggesting an involvement in early stages of the HR pathway. Involved in RAD51 foci formation in response to DNA damage suggesting an involvement in early stages of HR probably in the invasion step. Has an early function in DNA repair in facilitating phosphorylation of the checkpoint kinase CHEK2 and thereby transduction of the damage signal, leading to cell cycle arrest and HR activation. Participates in branch migration and HJ resolution and thus is important for processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex. Part of a PALB2-scaffolded HR complex containing BRCA2 and which is thought to play a role in DNA repair by HR. Protects RAD51 from ubiquitin-mediated degradation that is enhanced following DNA damage. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and XRCC3. Contributes to DNA cross-link resistance, sister chromatid cohesion and genomic stability. Involved in maintaining centrosome number in mitosis.^{[1] [2] [3] [4] [5] [6] [7] [8]}

References

1. ↑ 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
2. ↑ Bennett BT, Knight KL. Cellular localization of human Rad51C and regulation of ubiquitin-mediated proteolysis of Rad51. J Cell Biochem. 2005 Dec 15;96(6):1095-109. PMID:16215984 doi:10.1002/jcb.20640
3. ↑ Rodrigue A, Lafrance M, Gauthier MC, McDonald D, Hendzel M, West SC, Jasin M, Masson JY. Interplay between human DNA repair proteins at a unique double-strand break in vivo. EMBO J. 2006 Jan 11;25(1):222-31. PMID:16395335 doi:10.1038/sj.emboj.7600914
4. ↑ Badie S, Liao C, Thanasoula M, Barber P, Hill MA, Tarsounas M. RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation. J Cell Biol. 2009 May 18;185(4):587-600. PMID:19451272 doi:10.1083/jcb.200811079
5. ↑ Gildemeister OS, Sage JM, Knight KL. Cellular redistribution of Rad51 in response to DNA damage: novel role for Rad51C. J Biol Chem. 2009 Nov 13;284(46):31945-52. PMID:19783859 doi:10.1074/jbc.M109.024646
6. ↑ 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
7. ↑ 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
8. ↑ 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