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.
Ahel
Dragana
D
DNA Damage Response Laboratory, Clare Hall, London Research Institute, South Mimms EN6 3LD, UK.
Horejsí
Zuzana
Z
Wiechens
Nicola
N
Polo
Sophie E
SE
Garcia-Wilson
Elisa
E
Ahel
Ivan
I
Flynn
Helen
H
Skehel
Mark
M
West
Stephen C
SC
Jackson
Stephen P
SP
Owen-Hughes
Tom
T
Boulton
Simon J
SJ
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004249:DNA Damage; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047468:Immunoprecipitation; D007700:Kinetics; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D010692:Phleomycins / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011839:Radiation, Ionizing; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D002843:Chromatin; D004268:DNA-Binding Proteins; D050505:Mutant Proteins; D009707:Nucleosomes; D010692:Phleomycins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011994:Recombinant Proteins; D011064:Poly Adenosine Diphosphate Ribose; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; C543585:CHD1L protein, human