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J Cell Biol. 2012 Oct 15;199(2):235-49. doi: 10.1083/jcb.201112132. Epub 2012 Oct 8.

PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1.

Author information

1
Department of Toxicogenetics, Leiden University Medical Center, Leiden, Netherlands.

Abstract

The WD40-repeat protein DDB2 is essential for efficient recognition and subsequent removal of ultraviolet (UV)-induced DNA lesions by nucleotide excision repair (NER). However, how DDB2 promotes NER in chromatin is poorly understood. Here, we identify poly(ADP-ribose) polymerase 1 (PARP1) as a novel DDB2-associated factor. We demonstrate that DDB2 facilitated poly(ADP-ribosyl)ation of UV-damaged chromatin through the activity of PARP1, resulting in the recruitment of the chromatin-remodeling enzyme ALC1. Depletion of ALC1 rendered cells sensitive to UV and impaired repair of UV-induced DNA lesions. Additionally, DDB2 itself was targeted by poly(ADP-ribosyl)ation, resulting in increased protein stability and a prolonged chromatin retention time. Our in vitro and in vivo data support a model in which poly(ADP-ribosyl)ation of DDB2 suppresses DDB2 ubiquitylation and outline a molecular mechanism for PARP1-mediated regulation of NER through DDB2 stabilization and recruitment of the chromatin remodeler ALC1.

PMID:
23045548
PMCID:
PMC3471223
DOI:
10.1083/jcb.201112132
[Indexed for MEDLINE]
Free PMC Article

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