DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain

Mol Cell. 2004 Dec 22;16(6):991-1002. doi: 10.1016/j.molcel.2004.11.027.

Abstract

The postreplicative repair of double-strand breaks (DSBs) is thought to require sister chromatid cohesion, provided by the cohesin complex along the chromosome arms. A further specialized role for cohesin in DSB repair is suggested by its de novo recruitment to regions of DNA damage in mammals. Here, we show in budding yeast that a single DSB induces the formation of a approximately 100 kb cohesin domain around the lesion. Our analyses suggest that the primary DNA damage checkpoint kinases Mec1p and Tel1p phosphorylate histone H2AX to generate a large domain, which is permissive for cohesin binding. Cohesin binding to the phospho-H2AX domain is enabled by Mre11p, a component of a critical repair complex, and Scc2p, a component of the cohesin loading machinery that is necessary for sister chromatid cohesion. We also provide evidence that the DSB-induced cohesin domain functions in postreplicative repair.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Checkpoint Kinase 2
  • Chromosomal Proteins, Non-Histone
  • DNA / metabolism*
  • DNA Damage / physiology
  • DNA Repair / physiology*
  • Endodeoxyribonucleases / metabolism
  • Exodeoxyribonucleases / metabolism
  • Fungal Proteins
  • Gene Conversion / physiology
  • Histones / metabolism*
  • Nuclear Proteins / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Fungal Proteins
  • Histones
  • Nuclear Proteins
  • SCC2 protein, S cerevisiae
  • SCC4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • cohesins
  • gamma-H2AX protein, mouse
  • DNA
  • Checkpoint Kinase 2
  • Protein-Serine-Threonine Kinases
  • RAD53 protein, S cerevisiae
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • MRE11 protein, S cerevisiae