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Science 325 (5945): 1240-1243

Copyright © 2009 by the American Association for the Advancement of Science

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

Dragana Ahel,1 Zuzana Horejsí,1,* Nicola Wiechens,2,* Sophie E. Polo,3,* Elisa Garcia-Wilson,2 Ivan Ahel,4,5 Helen Flynn,6 Mark Skehel,6 Stephen C. West,5 Stephen P. Jackson,3 Tom Owen-Hughes,2 Simon J. Boulton1,{dagger}

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.

1 DNA Damage Response Laboratory, Clare Hall, London Research Institute, South Mimms EN6 3LD, UK.
2 Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
3 The Gurdon Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
4 Cancer Research UK, Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, UK.
5 Genetic Recombination Laboratory, Clare Hall, London Research Institute, South Mimms EN6 3LD, UK.
6 Protein Analysis and Proteomics Laboratory, Clare Hall, London Research Institute, South Mimms EN6 3LD, UK.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: Simon.boulton{at}cancer.org.uk

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