Individuals with BRCA2 mutations are predisposed to breast cancers owing to genome instability. To determine the functions of BRCA2, 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 BRCA2 were observed by EM. BRCA2 directed the binding of RAD51 recombinase to ssDNA, reduced the binding of RAD51 to duplex DNA and stimulated RAD51-mediated DNA strand exchange. These observations provide a molecular basis for the role of BRCA2 in the maintenance of genome stability.
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We thank T. Hyman (Max Planck Institute, Dresden) for providing the BAC modification cassettes. This work was supported by grants to S.C.W. (Cancer Research UK, the Breast Cancer Campaign, the Louis-Jeantet Foundation, Swiss Bridge and the European Research Council) and to J.D.G. and S.A.C. (US National Institutes of Health). T.T. was supported by the Alfred Benzon Foundation and the Carlsberg Foundation and S.L. by a European Molecular Biology Organization fellowship.
The authors declare no competing financial interests.
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Thorslund, T., McIlwraith, M., Compton, S. et al. The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA. Nat Struct Mol Biol 17, 1263–1265 (2010). https://doi.org/10.1038/nsmb.1905
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