Postreplicative recruitment of cohesin to double-strand breaks is required for DNA repair

Mol Cell. 2004 Dec 22;16(6):1003-15. doi: 10.1016/j.molcel.2004.11.026.

Abstract

Chromosome stability depends on accurate chromosome segregation and efficient DNA double-strand break (DSB) repair. Sister chromatid cohesion, established during S phase by the protein complex cohesin, is central to both processes. In the absence of cohesion, chromosomes missegregate and G2-phase DSB repair fails. Here, we demonstrate that G2-phase repair also requires the presence of cohesin at the damage site. Cohesin components are shown to be recruited to extended chromosome regions surrounding DNA breaks induced during G2. We find that in the absence of functional cohesin-loading proteins (Scc2/Scc4), the accumulation of cohesin at DSBs is abolished and repair is defective, even though sister chromatids are connected by S phase generated cohesion. Evidence is also provided that DSB induction elicits establishment of sister chromatid cohesion in G2, implicating that damage-recruited cohesin facilitates DNA repair by tethering chromatids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Cell Division / physiology
  • Chromatids / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA / metabolism*
  • DNA Damage / physiology*
  • DNA Repair / physiology*
  • Fungal Proteins
  • G2 Phase / physiology
  • Nuclear Proteins / metabolism*
  • Phosphoproteins
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Fungal Proteins
  • MCD1 protein, S cerevisiae
  • Nuclear Proteins
  • Phosphoproteins
  • SCC2 protein, S cerevisiae
  • SCC4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • cohesins
  • structural maintenance of chromosome protein 1
  • DNA