Interaction with the BRCA2 C-terminus Protects RAD51–DNA Filaments from Disassembly by BRC Repeats

摘要

BRCA2 is essential for DNA repair by homologous recombination via its interaction with RAD51, mediated by short motifs in the middle and at the C-terminus of its sequence. Here we report that a conserved 36-residue exon 27 sequence of human BRCA2 (BRCA2Exon 27) interacts with RAD51 through the specific recognition of oligomerised RAD51 ATPase domains. BRCA2Exon 27 binding stabilizes the RAD51 nucleoprotein filament against disassembly by BRC repeat 4. The protection is specific for RAD51 filaments formed on single-stranded DNA and is lost when BRCA2Exon 27 is phosphorylated on Ser3291. We propose that productive recombination results from the functional balance between the different modes of interaction with RAD51 of the BRC repeat and exon 27 regions of BRCA2. Our results further suggest a mechanism whereby CDK phosphorylation of BRCA2Exon 27 at the G2-M transition alters the balance in favor of RAD51 filament disassembly, thus terminating recombination.