The tumour suppressor complex BRCA1–BARD1 functions in the repair of DNA double-stranded breaks by homologous recombination. During this process, BRCA1–BARD1 facilitates the nucleolytic resection of DNA ends to generate a single-stranded template for the recruitment of another tumour suppressor complex, BRCA2–PALB2, and the recombinase RAD51. Here, by examining purified wild-type and mutant BRCA1–BARD1, we show that both BRCA1 and BARD1 bind DNA and interact with RAD51, and that BRCA1–BARD1 enhances the recombinase activity of RAD51. Mechanistically, BRCA1–BARD1 promotes the assembly of the synaptic complex, an essential intermediate in RAD51-mediated DNA joint formation. We provide evidence that BRCA1 and BARD1 are indispensable for RAD51 stimulation. Notably, BRCA1–BARD1 mutants with weakened RAD51 interactions show compromised DNA joint formation and impaired mediation of homologous recombination and DNA repair in cells. Our results identify a late role of BRCA1–BARD1 in homologous recombination, an attribute of the tumour suppressor complex that could be targeted in cancer therapy. The tumour suppressor complex BRCA1–BARD1, which facilitates the generation of a single-stranded DNA template during homologous recombination, also binds to the recombinase RAD51 and enhances its function. Two of the hereditary breast cancer susceptibility genes (BRCAs) act during the initial stages of recombinational DNA repair. BRCA1, together with BARD1, helps to form the single-stranded DNA that is then bound by another complex, BRCA2–PALB2, which facilitates loading of the central DNA strand exchange factor, RAD51. Patrick Sung and colleagues now show that BRCA1–BARD1 can also directly interact with RAD51 and stimulate the formation of the synaptic complex—a crucial intermediate that aligns the damaged and repair template DNA molecules. Because cancer cells depend on functioning DNA repair to thrive, targeting these factors may provide therapeutic value.

BRCA1–BARD1 promotes RAD51-mediated homologous DNA pairing