期刊
JOURNAL OF CELL BIOLOGY
卷 199, 期 2, 页码 235-249出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201112132
关键词
-
类别
资金
- Dutch Organization for Scientific Research (NWO): Veni Grant [917-96-120]
- Dutch Organization for Scientific Research (NWO): ZonMW Grant [40-00812-98-08031]
- European Molecular Biology Organization and Federation of the Societies of Biochemistry and Molecular Biology long-term fellowship
- Netherlands Genomics Initiative/Netherlands Organization for Scientific Research (NWO) [050-060-510]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据