BRCA2 stabilises RAD51 and DMC1 nucleoprotein filaments through a conserved interaction mode

Abstract

BRCA2 is essential for DNA repair by homologous recombination in mitosis and meiosis. It interacts with recombinases RAD51 and DMC1 to facilitate the formation of nucleoprotein filaments on resected DNA ends that catalyse recombination-mediated repair. BRCA2s BRC repeats bind and disrupt RAD51 and DMC1 filaments, whereas its PhePP motifs binds to recombinases in a manner that stabilises their nucleoprotein filaments. However, the mechanism of filament stabilisation has hitherto remained unknown. Here, we report the crystal structure of a BRCA2-DMC1 complex, revealing how PhePP motifs bind to recombinases. This novel mode of interaction is conserved for RAD51 and DMC1, which selectively bind to BRCA2s two distinct PhePP motifs. In both cases, BRCA2 PhePP motifs enhance the stability of nucleoprotein filaments, protecting them from BRC-mediated disruption. Hence, we report the structural basis of how BRCA2s PhePP motifs stabilise RAD51 and DMC1 nucleoprotein filaments for their essential roles in mitotic and meiotic recombination.