Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A (original) (raw)

Nature volume 391, pages 407–410 (1998)Cite this article

Abstract

The generation of a double-strand break in the Saccharomyces cerevisiae genome is a potentially catastrophic event that can induce cell-cycle arrest or ultimately result in loss of cell viability.The repair of such lesions is strongly dependent on proteins encoded by the RAD52 epistasis group of genes (RAD50-55, RAD57, MRE11, XRS2)1,2, as well as the RFA13,4 and RAD59 genes5. rad52 mutants exhibit the most severe phenotypic defects in double-strand break repair2, but almost nothing is known about the biochemical role of Rad52 protein. Rad51 protein promotes DNA strand exchange6,7,8 and acts similarly to RecA protein9. Yeast Rad52 protein interacts with Rad51 protein10,11, binds single-stranded DNA and stimulates annealing of complementary single-stranded DNA12. We find that Rad52 protein stimulates DNA strand exchange by targeting Rad51 protein to a complex of replication protein A (RPA) with single-stranded DNA. Rad52 protein affects an early step in the reaction, presynaptic filament formation, by overcoming the inhibitory effects of the competitor, RPA. Furthermore, stimulation is dependent on the concerted action of both Rad51 protein and RPA, implying that specific protein–protein interactions between Rad52 protein, Rad51 protein and RPA are required.

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Acknowledgements

We thank T. Ogawa for antibodies against Rad52 and Rad51 proteins, K. Adzuma for advice on the purification of Rad52 protein, E. Zaitsev for strains, and T. Ogawa, A. Shinohara, P. Sung and S. West for communication of unpublished results. This work was supported by grants from the NIH and from the Human Frontier Science Program (to S.C.K.).

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  1. Sections of Microbiology and of Molecular and Cellular Biology, University of California at Davis, Davis, 95616-8665, California , USA
    James H. New, Tomohiko Sugiyama, Elena Zaitseva & Stephen C. Kowalczykowski

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  1. James H. New
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  2. Tomohiko Sugiyama
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  3. Elena Zaitseva
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  4. Stephen C. Kowalczykowski
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Correspondence toStephen C. Kowalczykowski.

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New, J., Sugiyama, T., Zaitseva, E. et al. Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A.Nature 391, 407–410 (1998). https://doi.org/10.1038/34950

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