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

Sophie E Polo1, Abderrahmane Kaidi, Linda Baskcomb

  • 1Department of Biochemistry, The Gurdon Institute, University of Cambridge, Cambridge, UK.

The EMBO Journal
|August 10, 2010
PubMed

Insights

Chromodomain helicase DNA-binding protein 4 (CHD4) is crucial for DNA repair and cell survival. It regulates cell cycle progression by controlling p53 deacetylation, aiding genome stability.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Chromatin remodelling factor chromodomain helicase DNA-binding protein 4 (CHD4) is a key component of the NuRD transcriptional repressor complex.
  • The NuRD complex plays a role in gene regulation and cellular processes.

Purpose of the Study:

  • To investigate novel functions of CHD4 in the DNA-damage response (DDR) and cell-cycle control.
  • To elucidate the mechanisms by which CHD4 contributes to maintaining genome stability.

Main Methods:

  • Investigated CHD4's role in DNA damage response using biochemical and cellular assays.
  • Identified CHD4 as a phosphorylation target of ataxia-telangiectasia mutated (ATM) kinase.
  • Assessed the impact of CHD4 on DNA double-strand break repair and cell survival.
  • Examined CHD4's regulation of the G1/S cell-cycle transition via p53 deacetylation.

Main Results:

  • CHD4 mediates rapid poly(ADP-ribose)-dependent recruitment of the NuRD complex to DNA-damage sites.
  • CHD4 is phosphorylated by ATM, a key DDR kinase.
  • CHD4 promotes DNA double-strand break repair and enhances cell survival following DNA damage.
  • CHD4 regulates the G1/S cell-cycle transition by controlling p53 deacetylation.

Conclusions:

  • CHD4 has novel functions in DNA-damage response and cell-cycle control.
  • CHD4's role in DNA repair and cell-cycle regulation is critical for maintaining genome stability.
  • These findings provide new insights into the contribution of the NuRD complex to genome integrity.

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