PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1
The Journal of Cell Biology , Volume 199 - Issue 2 p. 235- 249
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.
|The Journal of Cell Biology|
|Organisation||Department of Pathology|
Pines, A, Vrouwe, M.G, Marteijn, J.A, Typas, D, Luijsterburg, M.S, Cansoy, M, … Mullenders, L.H.F. (2012). PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1. The Journal of Cell Biology, 199(2), 235–249. doi:10.1083/jcb.201112132