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Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1.

Science (New York, N.Y.) | Sep 4, 2009

Posttranslational modifications play key roles in regulating chromatin plasticity. Although various chromatin-remodeling enzymes have been described that respond to specific histone modifications, little is known about the role of poly[adenosine 5'-diphosphate (ADP)-ribose] in chromatin remodeling. Here, we identify a chromatin-remodeling enzyme, ALC1 (Amplified in Liver Cancer 1, also known as CHD1L), that interacts with poly(ADP-ribose) and catalyzes PARP1-stimulated nucleosome sliding. Our results define ALC1 as a DNA damage-response protein whose role in this process is sustained by its association with known DNA repair factors and its rapid poly(ADP-ribose)-dependent recruitment to DNA damage sites. Furthermore, we show that depletion or overexpression of ALC1 results in sensitivity to DNA-damaging agents. Collectively, these results provide new insights into the mechanisms by which poly(ADP-ribose) regulates DNA repair.

Pubmed ID: 19661379 RIS Download

Mesh terms: Adenosine Triphosphatases | Adenosine Triphosphate | Cell Line | Chromatin | Chromatin Assembly and Disassembly | DNA Damage | DNA Helicases | DNA Repair | DNA-Binding Proteins | Humans | Hydrogen Peroxide | Immunoprecipitation | Kinetics | Mutant Proteins | Nucleosomes | Phleomycins | Poly (ADP-Ribose) Polymerase-1 | Poly Adenosine Diphosphate Ribose | Poly(ADP-ribose) Polymerase Inhibitors | Poly(ADP-ribose) Polymerases | Protein Structure, Tertiary | Radiation, Ionizing | Recombinant Proteins

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Associated grants

  • Agency: Cancer Research UK, Id: 11224
  • Agency: Wellcome Trust, Id: 064414
  • Agency: Biotechnology and Biological Sciences Research Council, Id: A3549
  • Agency: Department of Health, Id: A5290
  • Agency: Cancer Research UK, Id:
  • Agency: Cancer Research UK, Id:
  • Agency: Cancer Research UK, Id:

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