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The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA

Nature Structural & Molecular Biology volume 17, pages 1263–1265 (2010)Cite this article

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Abstract

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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Figure 1: Purified BRCA2 binds specifically to ssDNA.
Figure 2: Binding of BRCA2 to tailed duplex DNA.
Figure 3: BRCA2 targets RAD51 to ssDNA and stimulates DNA strand exchange.

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Acknowledgements

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.

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  1. Tina Thorslund

    Present address: Present address: Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.,

Authors and Affiliations

  1. London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Hertfordshire, UK

    Tina Thorslund, Michael J McIlwraith, Sergey Lekomtsev, Mark Petronczki & Stephen C West

  2. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA

    Sarah A Compton & Jack D Griffith

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  1. Tina Thorslund
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  7. Stephen C West
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Contributions

T.T. and S.C.W. designed the study; S.L. and M.P. made the BRCA2 constructs; T.T. and M.J.M. made the RAD51 expression vectors, purified the proteins and carried out the biochemical analyses; and S.A.C. and J.D.G. visualized BRCA2 by electron microscopy. S.C.W. wrote the manuscript with contributions from T.T., S.A.C. and J.D.G.

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Correspondence to Stephen C West.

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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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