Extensive DNA damage-induced sumoylation contributes to replication and repair and acts in addition to the mec1 checkpoint

Mol Cell. 2012 Feb 10;45(3):422-32. doi: 10.1016/j.molcel.2011.11.028. Epub 2012 Jan 26.

Abstract

The cellular response to DNA damage employs multiple dynamic protein modifications to exert rapid and adaptable effects. Substantial work has detailed the roles of canonical checkpoint-mediated phosphorylation in this program. Recent studies have also implicated sumoylation in the DNA damage response; however, a systematic view of the contribution of sumoylation to replication and repair and its interplay with checkpoints is lacking. Here, using a biochemical screen in yeast, we establish that DNA damage-induced sumoylation occurs on a large scale. We identify MRX (Mre11-Rad50-Xrs2) as a positive regulator of this induction for a subset of repair targets. In addition, we find that defective sumoylation results in failure to complete replication of a damaged genome and impaired DNA end processing, highlighting the importance of the SUMO-mediated response in genome integrity. We also show that DNA damage-induced sumoylation does not require Mec1 checkpoint signaling, and the presence of both enables optimal DNA damage resistance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Cycle Checkpoints
  • DNA Damage
  • DNA Repair Enzymes / metabolism*
  • DNA Repair*
  • DNA Replication*
  • DNA-Binding Proteins / metabolism
  • Gene Knockout Techniques
  • Genome, Fungal
  • Genomic Instability
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Microbial Viability
  • Multiprotein Complexes / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sumoylation*

Substances

  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Multiprotein Complexes
  • Saccharomyces cerevisiae Proteins
  • MEC1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • DNA Repair Enzymes