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BRCA1 and BRCA2: different roles in a common pathway of genome protection

Abstract

The proteins encoded by the two major breast cancer susceptibility genes, BRCA1 and BRCA2, work in a common pathway of genome protection. However, the two proteins work at different stages in the DNA damage response (DDR) and in DNA repair. BRCA1 is a pleiotropic DDR protein that functions in both checkpoint activation and DNA repair, whereas BRCA2 is a mediator of the core mechanism of homologous recombination. The links between the two proteins are not well understood, but they must exist to explain the marked similarity of human cancer susceptibility that arises with germline mutations in these genes. As discussed here, the proteins work in concert to protect the genome from double-strand DNA damage during DNA replication.

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Figure 1: Molecular mechanisms of the DNA damage response.
Figure 2: BRCA1 and BRCA2 functional domains.
Figure 3: Homologous recombination at different types of DNA damage.
Figure 4: BRCA-deficient cells accumulate chromatid breaks and chromatid exchanges.

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Acknowledgements

The authors are supported by grants from the US National Cancer Institute and the Susan G. Komen For The Cure foundation.

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Roy, R., Chun, J. & Powell, S. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer 12, 68–78 (2012). https://doi.org/10.1038/nrc3181

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