Cohesin protects genes against γH2AX Induced by DNA double-strand breaks

PLoS Genet. 2012 Jan;8(1):e1002460. doi: 10.1371/journal.pgen.1002460. Epub 2012 Jan 19.


Chromatin undergoes major remodeling around DNA double-strand breaks (DSB) to promote repair and DNA damage response (DDR) activation. We recently reported a high-resolution map of γH2AX around multiple breaks on the human genome, using a new cell-based DSB inducible system. In an attempt to further characterize the chromatin landscape induced around DSBs, we now report the profile of SMC3, a subunit of the cohesin complex, previously characterized as required for repair by homologous recombination. We found that recruitment of cohesin is moderate and restricted to the immediate vicinity of DSBs in human cells. In addition, we show that cohesin controls γH2AX distribution within domains. Indeed, as we reported previously for transcription, cohesin binding antagonizes γH2AX spreading. Remarkably, depletion of cohesin leads to an increase of γH2AX at cohesin-bound genes, associated with a decrease in their expression level after DSB induction. We propose that, in agreement with their function in chromosome architecture, cohesin could also help to isolate active genes from some chromatin remodelling and modifications such as the ones that occur when a DSB is detected on the genome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Chondroitin Sulfate Proteoglycans / genetics*
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Chromatin Assembly and Disassembly / genetics*
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA Breaks, Double-Stranded / drug effects
  • DNA Damage
  • DNA Repair / genetics*
  • DNA-Binding Proteins
  • Gene Expression Regulation
  • Histones / genetics*
  • Histones / metabolism
  • Homologous Recombination
  • Humans
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacology
  • Transcription Initiation Site


  • Cell Cycle Proteins
  • Chondroitin Sulfate Proteoglycans
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • H2AX protein, human
  • Histones
  • Nuclear Proteins
  • Phosphoproteins
  • RAD21 protein, human
  • SMC3 protein, human
  • cohesins
  • Tamoxifen
  • afimoxifene