Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1.
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.
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 Adenosine Diphosphate Ribose, Poly(ADP-ribose) Polymerases, Protein Structure, Tertiary, Radiation, Ionizing, Recombinant Proteins
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 Adenosine Diphosphate Ribose, Poly(ADP-ribose) Polymerases, Protein Structure, Tertiary, Radiation, Ionizing, Recombinant Proteins
Science
Date: Sep. 04, 2009
PubMed ID: 19661379
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