SUMOylation regulates Rad18-mediated template switch

Nature. 2008 Dec 18;456(7224):915-20. doi: 10.1038/nature07587.


Replication by template switch is thought to mediate DNA damage-bypass and fillings of gaps. Gap-filling repair requires homologous recombination as well as Rad18- and Rad5-mediated proliferating cell nuclear antigen (PCNA) polyubiquitylation. However, it is unclear whether these processes are coordinated, and the physical evidence for Rad18-Rad5-dependent template switch at replication forks is still elusive. Here we show, using genetic and physical approaches, that in budding yeast (Saccharomyces cerevisiae) Rad18 is required for the formation of X-shaped sister chromatid junctions (SCJs) at damaged replication forks through a process involving PCNA polyubiquitylation and the ubiquitin-conjugating enzymes Mms2 and Ubc13. The Rad18-Mms2-mediated damage-bypass through SCJs requires the small ubiquitin-like modifier (SUMO)-conjugating enzyme Ubc9 and SUMOylated PCNA, and is coordinated with Rad51-dependent recombination events. We propose that the Rad18-Rad5-Mms2-dependent SCJs represent template switch events. Altogether, our results unmask a role for PCNA ubiquitylation and SUMOylation pathways in promoting transient damage-induced replication-coupled recombination events involving sister chromatids at replication forks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • DNA Damage
  • DNA Helicases
  • DNA Replication
  • DNA-Binding Proteins / metabolism*
  • Proliferating Cell Nuclear Antigen / metabolism
  • RecQ Helicases / genetics
  • RecQ Helicases / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sister Chromatid Exchange
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Templates, Genetic*
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Ubiquitin-Protein Ligases
  • Ubiquitination


  • DNA-Binding Proteins
  • MMS2 protein, S cerevisiae
  • Proliferating Cell Nuclear Antigen
  • RAD18 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • UBC13 protein, S cerevisiae
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Protein Ligases
  • Adenosine Triphosphatases
  • RAD5 protein, S cerevisiae
  • SGS1 protein, S cerevisiae
  • DNA Helicases
  • RecQ Helicases