Patrick Sung, D.Phil., Claudia Wiese, Ph.D.
Yale University, Colorado State University
A new study, funded in part by NIEHS, provides insight into the role the gene BRCA1 plays in DNA repair. Because mutations in BRCA1 increase risk of female breast and ovarian cancers, the findings could help researchers design drugs to combat these cancers.
In its normal state, BRCA1 genes produce proteins that repair breaks in DNA and suppress tumor formation. Previous studies showed that the BRCA1 protein joins another tumor suppressor protein known as BARD1 to help form single-stranded DNA during the initial stages of DNA repair. This single-stranded DNA attaches to the protein RAD51, which facilitates the resynthesis of the damaged region of DNA.
To learn more about the role of the BRCA1–BARD1 complex in DNA repair, the researchers developed a new method for expressing BRCA1–BARD1 in insect cells and then purifying the complex for biochemical analysis. Using this approach, they found that BRCA1–BARD1 can interact directly with RAD51 to promote the formation of an intermediate that is key for aligning damaged DNA with repair template DNA. The study also revealed that cells with BRCA1–BARD1 mutants had weakened RAD51 interactions and impaired DNA repair. By identifying a new role for the BRCA1–BARD1 complex in the later stages of DNA repair, the study reveals a potential new target for future cancer therapies.
Citation: Zhao W, Steinfeld JB, Liang F, Chen X, Maranon DG, Jian Ma C, Kwon Y, Rao T, Wang W, Sheng C, Song X, Deng Y, Jimenez-Sainz J, Lu L, Jensen RB, Xiong Y, Kupfer GM, Wiese C, Greene EC, Sung P. 2017. BRCA1-BARD1 promotes RAD51-mediated homologous DNA pairing. Nature 550(7676):360-365.