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 language | English |
|---|---|
| Pages (from-to) | 3130-3139 |
| Number of pages | 10 |
| Journal | EMBO Journal |
| Volume | 29 |
| Issue number | 18 |
| Early online date | 6 Aug 2010 |
| DOIs | |
| Publication status | Published - 15 Sept 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