Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis

EMBO J. 2013 Mar 6;32(5):742-55. doi: 10.1038/emboj.2013.9. Epub 2013 Feb 8.

Abstract

Completion of DNA replication needs to be ensured even when challenged with fork progression problems or DNA damage. PCNA and its modifications constitute a molecular switch to control distinct repair pathways. In yeast, SUMOylated PCNA (S-PCNA) recruits Srs2 to sites of replication where Srs2 can disrupt Rad51 filaments and prevent homologous recombination (HR). We report here an unexpected additional mechanism by which S-PCNA and Srs2 block the synthesis-dependent extension of a recombination intermediate, thus limiting its potentially hazardous resolution in association with a cross-over. This new Srs2 activity requires the SUMO interaction motif at its C-terminus, but neither its translocase activity nor its interaction with Rad51. Srs2 binding to S-PCNA dissociates Polδ and Polη from the repair synthesis machinery, thus revealing a novel regulatory mechanism controlling spontaneous genome rearrangements. Our results suggest that cycling cells use the Siz1-dependent SUMOylation of PCNA to limit the extension of repair synthesis during template switch or HR and attenuate reciprocal DNA strand exchanges to maintain genome stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Damage / genetics
  • DNA Damage / radiation effects
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Polymerase II / genetics
  • DNA Polymerase II / metabolism
  • DNA Polymerase III / genetics
  • DNA Polymerase III / metabolism
  • DNA Repair / genetics*
  • DNA Repair / radiation effects
  • DNA Replication / genetics
  • DNA Replication / radiation effects
  • Genomic Instability
  • Homologous Recombination*
  • Mutation / genetics
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism
  • SUMO-1 Protein / genetics
  • SUMO-1 Protein / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sumoylation
  • Ultraviolet Rays / adverse effects

Substances

  • Proliferating Cell Nuclear Antigen
  • SUMO-1 Protein
  • Saccharomyces cerevisiae Proteins
  • SRS2 protein, S cerevisiae
  • RAD51 protein, S cerevisiae
  • Rad51 Recombinase
  • DNA Polymerase II
  • DNA Polymerase III
  • DNA Helicases