Cohesin association to replication sites depends on rad50 and promotes fork restart

Mol Cell. 2012 Oct 12;48(1):98-108. doi: 10.1016/j.molcel.2012.07.004. Epub 2012 Aug 9.

Abstract

The cohesin complex holds together newly replicated chromatids and is involved in diverse pathways that preserve genome integrity. We show that in budding yeast, cohesin is transiently recruited to active replication origins, and it spreads along DNA as forks progress. When DNA synthesis is impeded, cohesin accumulates at replication sites and is critical for the recovery of stalled forks. Cohesin enrichment at replication forks does not depend on γH2A(X) formation, which differs from its loading requirements at DNA double-strand breaks (DSBs). However, cohesin localization is largely reduced in rad50Δ mutants and in cells lacking both Mec1 and Tel1 checkpoint kinases. Interestingly, cohesin loading at replication sites depends on the structural features of Rad50 that are important for bridging sister chromatids, including the CXXC hook domain and the length of the coiled-coil extensions. Together, these data reveal a function for cohesin in the maintenance of genome integrity during S phase.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • DNA Replication / physiology*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Genes, Fungal
  • Histones / metabolism
  • Hydroxyurea / pharmacology
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mutation
  • Protein Serine-Threonine Kinases / metabolism
  • S Phase
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Stress, Physiological

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • RAD50 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • cohesins
  • gammaH2AX protein, S cerevisiae
  • MEC1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • Hydroxyurea

Associated data

  • GEO/GSE21014
  • GEO/GSE33686
  • GEO/GSE39078