Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks

Cell Rep. 2019 Dec 3;29(10):3160-3172.e4. doi: 10.1016/j.celrep.2019.10.123.

Abstract

Replication of a damaged DNA template can threaten the integrity of the genome, requiring the use of various mechanisms to tolerate DNA lesions. The Smc5/6 complex, together with the Nse2/Mms21 SUMO ligase, plays essential roles in genome stability through undefined tasks at damaged replication forks. Various subunits within the Smc5/6 complex are substrates of Nse2, but we currently do not know the role of these modifications. Here we show that sumoylation of Smc5 is targeted to its coiled-coil domain, is upregulated by replication fork damage, and participates in bypass of DNA lesions. smc5-KR mutant cells display defects in formation of sister chromatid junctions and higher translesion synthesis. Also, we provide evidence indicating that Smc5 sumoylation modulates Mph1-dependent fork regression, acting synergistically with other pathways to promote chromosome disjunction. We propose that sumoylation of Smc5 enhances physical remodeling of damaged forks, avoiding the use of a more mutagenic tolerance pathway.

Keywords: DNA damage tolerance; DNA replication; Mms21; Mph1; Nse2; SUMO; Smc5; chromosome; fork regression; yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics*
  • Chromatids / genetics
  • Chromosomes / genetics
  • DNA / genetics
  • DNA Damage / genetics
  • DNA Repair / genetics
  • DNA Replication / genetics*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics*
  • Sumoylation / genetics*

Substances

  • Cell Cycle Proteins
  • SMC5 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • DNA