The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA

Abstract

Individuals with BRCA2 mutations are predisposed to breast cancers owing to genome instability. To determine the functions of BRCA 2, the human protein was purified. It was found to bind selectively to single-stranded DNA (ssDNA), and to ssDNA in tailed duplexes and replication fork structures. Monomeric and dimeric forms of BRCA 2 were observed by EM. BRCA 2 directed the binding of RA D51 recombinase to ssDNA, reduced the binding of RA D51 to duplex DNA and stimulated RA D51-mediated DNA strand exchange. These observations provide a molecular basis for the role of BRCA 2 in the maintenance of genome stability.