The Post-Synaptic Function of Brca2

Abstract

Homologous Recombination (HR) is a high-fidelity process with a range of biologic functions from generation of genetic diversity to repair of DNA double-strand breaks (DSBs). In mammalian cells, BRCA2 facilitates the polymerization of RAD51 onto ssDNA to form a presynaptic nucleoprotein filament. This filament can then strand invade a homologous dsDNA to form the displacement loop (D-loop) structure leading to the eventual DSB repair. Here, we have found that RAD51 in stoichiometric excess over ssDNA can cause D-loop disassembly in vitro; furthermore, we show that this RAD51 activity is countered by BRCA2. These results demonstrate that BRCA2 may have a previously unexpected activity: regulation of HR at a post-synaptic stage by modulating RAD51-mediated D-loop dissociation. Our in vitro results suggest a mechanistic underpinning of homeostasis between RAD51 and BRCA2, which is an important factor of HR in mammalian cells.