Dynamic regulatory interactions of rad51, rad52, and replication protein-a in recombination intermediates

J Mol Biol. 2009 Jul 3;390(1):45-55. doi: 10.1016/j.jmb.2009.05.009. Epub 2009 May 13.

Abstract

Rad51, Rad52, and replication protein-A (RPA) play crucial roles in the repair of DNA double-strand breaks in Saccharomyces cerevisiae. Rad51 mediates DNA strand exchange, a key reaction in DNA recombination. Rad52 recruits Rad51 into single-stranded DNAs (ssDNAs) that are saturated with RPA. Rad52 also promotes annealing of ssDNA strands that are complexed with RPA. Specific protein-protein interactions are involved in these reactions. Here we report new biochemical characteristics of these protein interactions. First, Rad52-RPA interaction requires multiple molecules of RPA to be associated with ssDNA, suggesting that multiple contacts between the Rad52 ring and RPA-ssDNA filament are needed for stable binding. Second, RPA-t11, which is a recombination-deficient mutant of RPA, displays a defect in interacting with Rad52 in the presence of salt above 50 mM, explaining the defect in Rad52-mediated ssDNA annealing in the presence of this mutation. Third, ssDNA annealing promoted by Rad52 is preceded by aggregation of multiple RPA-ssDNA complexes with Rad52, and Rad51 inhibits this aggregation. These results suggest a regulatory role for Rad51 that suppresses ssDNA annealing and facilitates DNA strand invasion. Finally, the Rad51-double-stranded DNA complex disrupts Rad52-RPA interaction in ssDNA and titrates Rad52 from RPA. This suggests an additional regulatory role for Rad51 following DNA strand invasion, where Rad51-double-stranded DNA may inhibit illegitimate second-end capture to ensure the error-free repair of a DNA double-strand break.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / metabolism
  • DNA Repair*
  • DNA, Single-Stranded / metabolism
  • Models, Biological
  • Protein Binding
  • Protein Interaction Mapping*
  • Rad51 Recombinase / metabolism*
  • Rad52 DNA Repair and Recombination Protein / metabolism*
  • Recombination, Genetic*
  • Replication Protein A / metabolism*
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

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