Poly(ADP-ribose)-Dependent Regulation of DNA Repair by the Chromatin Remodeling Enzyme ALC1

• Published in: Science (American Association for the Advancement of Science) 2009-09, Vol.325 (5945), p.1240-1243
• Main Authors: Ahel, Dragana, Hořejší, Zuzana, Wiechens, Nicola, Polo, Sophie E, Garcia-Wilson, Elisa, Ahel, Ivan, Flynn, Helen, Skehel, Mark, West, Stephen C, Jackson, Stephen P, Owen-Hughes, Tom, Boulton, Simon J
• Format: Article
• Language: English
• Subjects: Adenosine triphosphatases; Adenosine Triphosphatases - metabolism; Adenosine Triphosphate - metabolism; Biological and medical sciences; Cell Line; Cell lines; Chromatin; Chromatin - metabolism; Chromatin Assembly and Disassembly; DNA; DNA Damage; DNA Helicases - chemistry; DNA Helicases - genetics; DNA Helicases - metabolism; DNA polymerase; DNA Repair; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Enzymes; Fundamental and applied biological sciences. Psychology; Humans; Hydrogen Peroxide - pharmacology; Immunoprecipitation; Kinetics; Life Sciences; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Mutant Proteins - chemistry; Mutant Proteins - metabolism; Nucleosomes; 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; Proteins; Radiation, Ionizing; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Renovations
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1177321

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.