Stapled peptide SP30 in complex with humanised RadA mutant HumRadA22

Tumor suppressor protein that maintains genome stability primarily by repairing damaged DNA through homologous recombination (HR) ^[1–17]. 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 ^{[1, 2, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16]}. BRCA2 nucleates and stabilizes RAD51 on ssDNA directly and delivers RAD51 to ssDNA-double-stranded DNA (dsDNA) junctions by sliding along dsDNA backbone ^{[2, 10, 16]}.

RAD51 targeting to ssDNA promotes removal of replication protein-A (RPA) from ssDNA and stabilization of RAD51-ssDNA filaments by blocking ATP hydrolysis ^[13]. 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 ^[18]. Required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability ^[19].

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 ^[19]. Also promotes RAD51 loading to telomeric regions, facilitating telomere replication and capping ^[20]. 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 ^[21].

Also promotes homologous recombination by inactivating the FIGNL1-FIRRM complex to protect RAD51 filament from premature disassembly ^[17]. Together with NPM1, may also regulate centrosome duplication ^[22]