Overlapping mechanisms promote postsynaptic RAD-51 filament disassembly during meiotic double-strand break repair

Mol Cell. 2010 Jan 29;37(2):259-72. doi: 10.1016/j.molcel.2009.12.026.

Abstract

Homologous recombination (HR) is essential for repair of meiotic DNA double-strand breaks (DSBs). Although the mechanisms of RAD-51-DNA filament assembly and strand exchange are well characterized, the subsequent steps of HR are less well defined. Here, we describe a synthetic lethal interaction between the C. elegans helicase helq-1 and RAD-51 paralog rfs-1, which results in a block to meiotic DSB repair after strand invasion. Whereas RAD-51-ssDNA filaments assemble at meiotic DSBs with normal kinetics in helq-1, rfs-1 double mutants, persistence of RAD-51 foci and genetic interactions with rtel-1 suggest a failure to disassemble RAD-51 from strand invasion intermediates. Indeed, purified HELQ-1 and RFS-1 independently bind to and promote the disassembly of RAD-51 from double-stranded, but not single-stranded, DNA filaments via distinct mechanisms in vitro. These results indicate that two compensating activities are required to promote postsynaptic RAD-51 filament disassembly, which are collectively essential for completion of meiotic DSB repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology*
  • DNA Breaks, Double-Stranded*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Helicases / physiology
  • DNA Repair / genetics
  • DNA Repair / physiology*
  • DNA, Helminth / metabolism
  • DNA, Single-Stranded / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Meiosis*
  • Mutation
  • Rad51 Recombinase / metabolism*
  • Recombination, Genetic

Substances

  • Caenorhabditis elegans Proteins
  • DNA, Helminth
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • RFS-1 protein, C elegans
  • Rad51 Recombinase
  • rad-51 protein, C elegans
  • HELQ-1 protein, C elegans
  • DNA Helicases