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

2.50
Hdl Handle:
http://hdl.handle.net/10541/87560
Title:
Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1.
Authors:
Ahel, Dragana; Horejsí, 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
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.
Affiliation:
DNA Damage Response Laboratory, Clare Hall, London Research Institute, South Mimms EN6 3LD, UK.
Citation:
Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1. 2009, 325 (5945):1240-3 Science
Journal:
Science
Issue Date:
4-Sep-2009
URI:
http://hdl.handle.net/10541/87560
DOI:
10.1126/science.1177321
PubMed ID:
19661379
Type:
Article
Language:
en
ISSN:
1095-9203
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorAhel, Draganaen
dc.contributor.authorHorejsí, Zuzanaen
dc.contributor.authorWiechens, Nicolaen
dc.contributor.authorPolo, Sophie Een
dc.contributor.authorGarcia-Wilson, Elisaen
dc.contributor.authorAhel, Ivanen
dc.contributor.authorFlynn, Helenen
dc.contributor.authorSkehel, Marken
dc.contributor.authorWest, Stephen Cen
dc.contributor.authorJackson, Stephen Pen
dc.contributor.authorOwen-Hughes, Tomen
dc.contributor.authorBoulton, Simon Jen
dc.date.accessioned2009-12-08T12:14:34Z-
dc.date.available2009-12-08T12:14:34Z-
dc.date.issued2009-09-04-
dc.identifier.citationPoly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1. 2009, 325 (5945):1240-3 Scienceen
dc.identifier.issn1095-9203-
dc.identifier.pmid19661379-
dc.identifier.doi10.1126/science.1177321-
dc.identifier.urihttp://hdl.handle.net/10541/87560-
dc.description.abstractPosttranslational 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.en
dc.language.isoenen
dc.subject.meshAdenosine Triphosphatases-
dc.subject.meshAdenosine Triphosphate-
dc.subject.meshCell Line-
dc.subject.meshChromatin-
dc.subject.meshChromatin Assembly and Disassembly-
dc.subject.meshDNA Damage-
dc.subject.meshDNA Helicases-
dc.subject.meshDNA Repair-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshHumans-
dc.subject.meshHydrogen Peroxide-
dc.subject.meshImmunoprecipitation-
dc.subject.meshKinetics-
dc.subject.meshMutant Proteins-
dc.subject.meshNucleosomes-
dc.subject.meshPhleomycins-
dc.subject.meshPoly Adenosine Diphosphate Ribose-
dc.subject.meshPoly(ADP-ribose) Polymerases-
dc.subject.meshProtein Structure, Tertiary-
dc.subject.meshRadiation, Ionizing-
dc.subject.meshRecombinant Proteins-
dc.titlePoly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1.en
dc.typeArticleen
dc.contributor.departmentDNA Damage Response Laboratory, Clare Hall, London Research Institute, South Mimms EN6 3LD, UK.en
dc.identifier.journalScienceen

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