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

Science. 2009 Sep 4;325(5945):1240-3. doi: 10.1126/science.1177321. Epub 2009 Aug 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Cell Line
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly*
  • DNA Damage
  • DNA Helicases / chemistry
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Repair*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Immunoprecipitation
  • Kinetics
  • Mutant Proteins / chemistry
  • Mutant Proteins / metabolism
  • Nucleosomes / metabolism
  • Phleomycins / pharmacology
  • Poly (ADP-Ribose) Polymerase-1
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protein Structure, Tertiary
  • Radiation, Ionizing
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Mutant Proteins
  • Nucleosomes
  • Phleomycins
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Recombinant Proteins
  • Poly Adenosine Diphosphate Ribose
  • Adenosine Triphosphate
  • Hydrogen Peroxide
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Adenosine Triphosphatases
  • DNA Helicases
  • CHD1L protein, human