| First Author | Zhao W | Year | 2017 |
| Journal | Nature | Volume | 550 |
| Issue | 7676 | Pages | 360-365 |
| PubMed ID | 28976962 | Mgi Jnum | J:336816 |
| Mgi Id | MGI:7466443 | Doi | 10.1038/nature24060 |
| Citation | Zhao W, et al. (2017) BRCA1-BARD1 promotes RAD51-mediated homologous DNA pairing. Nature 550(7676):360-365 |
| abstractText | 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. |
