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. {Experimental EvidencePubMed:14716019, Experimental EvidencePubMed:16215984, Experimental EvidencePubMed:16395335, Experimental EvidencePubMed:19451272, Experimental EvidencePubMed:19783859, Experimental EvidencePubMed:20413593, Experimental EvidencePubMed:23108668, Experimental EvidencePubMed:23149936}.
Fanconi anemia complementation group O (FANCO) [MIM:613390]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. {Experimental EvidencePubMed:20400963, Experimental EvidencePubMed:24141787}. Note=The disease is caused by variants affecting the gene represented in this entry. Breast-ovarian cancer, familial, 3 (BROVCA3) [MIM:613399]: A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate. {Experimental EvidencePubMed:20400964, Experimental EvidencePubMed:21990120, Experimental EvidencePubMed:24141787}. Note=The disease is caused by variants affecting the gene represented in this entry.
National and Kapodistrian University of Athens
Department of Biology
Biophysics & Bioinformatics Laboratory