Breast cancer type 2 susceptibility protein

Tumor suppressor protein that maintains genome stability primarily by repairing damaged DNA through homologous recombination (HR) (PubMed:11239456, PubMed:12442171, PubMed:15115758, PubMed:15199141, PubMed:15671039, PubMed:15937124, PubMed:17515903, PubMed:17515904, PubMed:18317453, PubMed:19303847, PubMed:20729832, PubMed:20729858, PubMed:20729859, PubMed:21719596, PubMed:27941124, PubMed:37499663, PubMed:37515771). Facilitates the repair of double-strand breaks (DSBs) by binding and mediating the loading of the RAD51 protein onto single-stranded DNA (ssDNA), thereby promoting the activity of RAD51, which catalyzes DNA strand exchange (PubMed:11239456, PubMed:12442171, PubMed:15937124, PubMed:17515903, PubMed:17515904, PubMed:18317453, PubMed:19303847, PubMed:20729832, PubMed:20729858, PubMed:20729859, PubMed:27941124, PubMed:37499663). BRCA2 nucleates and stabilizes RAD51 on ssDNA directly and delivers RAD51 to ssDNA-double-stranded DNA (dsDNA) junctions by sliding along dsDNA backbone (PubMed:12442171, PubMed:19303847, PubMed:37499663). RAD51 targeting to ssDNA promotes removal of replication protein-A (RPA) from ssDNA and stabilization of RAD51-ssDNA filaments by blocking ATP hydrolysis (PubMed:20729859). May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity (PubMed:24485656). Required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability (PubMed:24896180). Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180). Also promotes RAD51 loading to telomeric regions, facilitating telomere replication and capping (PubMed:21076401). Also required for homologous recombination during meiosis by promoting the recruitment of RAD51 and DMC1 recombinases to meiotic DSB sites, enabling proper chromosome pairing and crossing over (PubMed:26976601). Also promotes homologous recombination by inactivating the FIGNL1-FIRRM complex to protect RAD51 filament from premature disassembly (PubMed:37515771). Together with NPM1, may also regulate centrosome duplication (PubMed:21084279)