Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A

Nature. 1998 Jan 22;391(6665):407-10. doi: 10.1038/34950.

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), as well as the RFA1 and RAD59 genes. rad52 mutants exhibit the most severe phenotypic defects in double-strand break repair, but almost nothing is known about the biochemical role of Rad52 protein. Rad51 protein promotes DNA strand exchange and acts similarly to RecA protein. Yeast Rad52 protein interacts with Rad51 protein, binds single-stranded DNA and stimulates annealing of complementary single-stranded DNA. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • DNA, Single-Stranded / metabolism
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Rad51 Recombinase
  • Rad52 DNA Repair and Recombination Protein
  • Recombination, Genetic*
  • Replication Protein A
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins

Substances

  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • RAD52 protein, S cerevisiae
  • Rad52 DNA Repair and Recombination Protein
  • Replication Protein A
  • Saccharomyces cerevisiae Proteins
  • RAD51 protein, S cerevisiae
  • Rad51 Recombinase