JOURNAL ARTICLE

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

Alex Pines, Mischa G Vrouwe, Jurgen A Marteijn, Dimitris Typas, Martijn S Luijsterburg, Medine Cansoy, Paul Hensbergen, André Deelder, Anton de Groot, Syota Matsumoto, Kaoru Sugasawa, Nicolas Thoma, Wim Vermeulen, Harry Vrieling, Leon Mullenders
Journal of Cell Biology 2012 October 15, 199 (2): 235-49
23045548
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.

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