Sgs1's roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6

Genes Dev. 2016 Jun 1;30(11):1339-56. doi: 10.1101/gad.278275.116.


The RecQ helicase Sgs1 plays critical roles during DNA repair by homologous recombination, from end resection to Holliday junction (HJ) dissolution. Sgs1 has both pro- and anti-recombinogenic roles, and therefore its activity must be tightly regulated. However, the controls involved in recruitment and activation of Sgs1 at damaged sites are unknown. Here we show a two-step role for Smc5/6 in recruiting and activating Sgs1 through SUMOylation. First, auto-SUMOylation of Smc5/6 subunits leads to recruitment of Sgs1 as part of the STR (Sgs1-Top3-Rmi1) complex, mediated by two SUMO-interacting motifs (SIMs) on Sgs1 that specifically recognize SUMOylated Smc5/6. Second, Smc5/6-dependent SUMOylation of Sgs1 and Top3 is required for the efficient function of STR. Sgs1 mutants impaired in recognition of SUMOylated Smc5/6 (sgs1-SIMΔ) or SUMO-dead alleles (sgs1-KR) exhibit unprocessed HJs at damaged replication forks, increased crossover frequencies during double-strand break repair, and severe impairment in DNA end resection. Smc5/6 is a key regulator of Sgs1's recombination functions.

Keywords: Sgs1–Top3; Smc complexes; Smc5/6; genome stability; homologous recombination.

MeSH terms

  • Amino Acid Motifs
  • Cell Cycle Proteins / metabolism*
  • Crossing Over, Genetic
  • DNA Damage / genetics
  • DNA End-Joining Repair / genetics
  • DNA, Cruciform / metabolism*
  • Mutation
  • RecQ Helicases / genetics
  • RecQ Helicases / metabolism*
  • Recombination, Genetic / genetics
  • SUMO-1 Protein / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sumoylation


  • Cell Cycle Proteins
  • DNA, Cruciform
  • Mms21 protein, S cerevisiae
  • SMC5 protein, S cerevisiae
  • SMC6 protein, S cerevisiae
  • SUMO-1 Protein
  • Saccharomyces cerevisiae Proteins
  • TOP3 protein, S cerevisiae
  • SGS1 protein, S cerevisiae
  • RecQ Helicases