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

Article Details

Citation

Ahel D, Horejsi Z, Wiechens N, Polo SE, Garcia-Wilson E, Ahel I, Flynn H, Skehel M, West SC, Jackson SP, Owen-Hughes T, Boulton SJ

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.

PubMed ID
19661379 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Poly [ADP-ribose] polymerase 1P09874Details