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. (2009) Poly(ADP-ribose)-Dependent Regulation of DNA Repair by the Chromatin Remodeling Enzyme ALC1. Science 325, 1240-3. *These authors contributed equally to this work.

Post-translational 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(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.