Regulation of DNA-damage responses and cell-cycle progression by the chromatin remodelling factor CHD4

Sophie E Polo, Abderrahmane Kaidi, Linda Baskcomb, Yaron Galanty, Stephen P Jackson

Research output: Contribution to journalArticle (Academic Journal)peer-review

225 Citations (Scopus)

Abstract

The chromatin remodelling factor chromodomain helicase DNA-binding protein 4 (CHD4) is a catalytic subunit of the NuRD transcriptional repressor complex. Here, we reveal novel functions for CHD4 in the DNA-damage response (DDR) and cell-cycle control. We show that CHD4 mediates rapid poly(ADP-ribose)-dependent recruitment of the NuRD complex to DNA-damage sites, and we identify CHD4 as a phosphorylation target for the apical DDR kinase ataxia-telangiectasia mutated. Functionally, we show that CHD4 promotes repair of DNA double-strand breaks and cell survival after DNA damage. In addition, we show that CHD4 acts as an important regulator of the G1/S cell-cycle transition by controlling p53 deacetylation. These results provide new insights into how the chromatin remodelling complex NuRD contributes to maintaining genome stability.
Original languageEnglish
Pages (from-to)3130-3139
Number of pages10
JournalEMBO Journal
Volume29
Issue number18
Early online date6 Aug 2010
DOIs
Publication statusPublished - 15 Sep 2010

Keywords

  • Animals
  • Autoantigens
  • Blotting, Western
  • Cell Cycle
  • Cell Cycle Proteins
  • Chromatin Assembly and Disassembly
  • DNA Damage
  • DNA Helicases
  • DNA-Binding Proteins
  • Fluorescent Antibody Technique
  • Histones
  • Humans
  • Immunoprecipitation
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex
  • Mice
  • Mice, Knockout
  • Phosphorylation
  • Poly Adenosine Diphosphate Ribose
  • Protein-Serine-Threonine Kinases
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins

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