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Human BRCA2 protein promotes RAD51 filament formation on RPA-covered single-stranded DNA

Nature Structural & Molecular Biology volume 17, pages 1260–1262 (2010)Cite this article

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Abstract

BRCA2 is a tumor suppressor that functions in homologous recombination, a key genomic integrity pathway. BRCA2 interacts with RAD51, the central protein of recombination, which forms filaments on single-stranded DNA (ssDNA) to perform homology search and DNA strand invasion. We report the purification of full-length human BRCA2 and show that it binds to ∼6 RAD51 molecules and promotes RAD51 binding to ssDNA coated by replication protein A (RPA), in a manner that is stimulated by DSS1.

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Figure 1: Purification of human BRCA2 and interaction with RAD51.
Figure 2: BRCA2 promotes RAD51 binding to RPA-covered gapped DNA.

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Acknowledgements

We thank M. Wold (University of Iowa) and P. Sung (Yale University) for antibodies and overexpression vectors, and S. Kowalczykowski for sharing unpublished results and for comments, as well as N. Hunter, K. Ehmsen, E. Schwartz, W. Wright, X.-P. Zhang, D. Meyer, J. Sneeden and C. Fasching for critical comments on the manuscript. This work was supported by grants from the Tobacco-Related Disease Research Program (17FT-0046), US National Institutes of Health (GM58015, CA92276), US Department of Defense (DAMD17-00-1-0187), Susan G. Komen Breast Cancer Foundation (BCTR0201259) and University of California Davis Cancer Center.

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Author notes

  1. Tammy Doty & Bryan Gibson

    Present address: Present addresses: Novozymes, Inc., Davis, California, USA (T.D.); Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA (B.G.).,

Authors and Affiliations

  1. Department of Microbiology, University of California, Davis, Davis, California, USA

    Jie Liu, Tammy Doty, Bryan Gibson & Wolf-Dietrich Heyer

  2. Department of Molecular and Cellular Biology, University of California, Davis, Davis, California, USA

    Wolf-Dietrich Heyer

Authors
  1. Jie Liu
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  2. Tammy Doty
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  4. Wolf-Dietrich Heyer
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Contributions

J.L. designed, performed and analyzed all experiments and helped write the manuscript. T.D., J.L. and B.G. purified BRCA2 and DSS1. W.-D.H. conceived the project, designed experiments, contributed to data analysis and wrote the manuscript with J.L., with contributions from all authors.

Corresponding author

Correspondence to Wolf-Dietrich Heyer.

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The authors declare no competing financial interests.

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Liu, J., Doty, T., Gibson, B. et al. Human BRCA2 protein promotes RAD51 filament formation on RPA-covered single-stranded DNA. Nat Struct Mol Biol 17, 1260–1262 (2010). https://doi.org/10.1038/nsmb.1904

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