Unraveling the mechanism of BRCA2 in homologous recombination

Abstract

BRCA2 is the product of a breast cancer susceptibility gene in humans and the founding member of an emerging family of proteins present throughout the eukaryotic domain that serve in homologous recombination. The function of BRCA2 in recombination is to control RAD51, a protein that catalyzes homologous pairing and DNA strand exchange. By physically interacting with both RAD51 and single-stranded DNA, BRCA2 mediates delivery of RAD51 preferentially to sites of single-stranded DNA (ssDNA) exposed as a result of DNA damage or replication problems. Through its action, BRCA2 helps restore and maintain integrity of the genome. This review highlights recent studies on BRCA2 and its orthologs that have begun to illuminate the molecular mechanisms by which these proteins control homologous recombination.

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Figure 1: DNA repair by homologous recombination.
Figure 2: BRCA2 organization and DBD domain structure.

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Acknowledgements

The author is grateful to L. Symington (Columbia University) and laboratory members M. Kojic, Q. Zhou and N. Mazloum for stimulating conversations. Apologies are extended to colleagues whose work was not cited because of space limitations. Research in the author's laboratory is supported by grants GM042482 and GM079859 from the US National Institutes of Health.

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Correspondence to William K Holloman.

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Holloman, W. Unraveling the mechanism of BRCA2 in homologous recombination. Nat Struct Mol Biol 18, 748–754 (2011). https://doi.org/10.1038/nsmb.2096

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