title: ATP-dependent chromatin remodeling by Cockayne syndrome protein B and NAP1-like histone chaperones is required for efficient transcription-coupled DNA repair.
abstract: The Cockayne syndrome complementation group B (CSB) protein is essential for transcription-coupled DNA repair, and mutations in CSB are associated with Cockayne syndrome--a devastating disease with complex clinical features, including the appearance of premature aging, sun sensitivity, and numerous neurological and developmental defects. CSB belongs to the SWI2/SNF2 ATP-dependent chromatin remodeler family, but the extent to which CSB remodels chromatin and whether this activity is utilized in DNA repair is unknown. Here, we show that CSB repositions nucleosomes in an ATP-dependent manner in vitro and that this activity is greatly enhanced by the NAP1-like histone chaperones, which we identify as new CSB-binding partners. By mapping functional domains and analyzing CSB derivatives, we demonstrate that chromatin remodeling by the combined activities of CSB and the NAP1-like chaperones is required for efficient transcription-coupled DNA repair. Moreover, we show that chromatin remodeling and repair protein recruitment mediated by CSB are separable activities. The collaboration that we observed between CSB and the NAP1-like histone chaperones adds a new dimension to our understanding of the ways in which ATP-dependent chromatin remodelers and histone chaperones can regulate chromatin structure. Taken together, the results of this study offer new insights into the functions of chromatin remodeling by CSB in transcription-coupled DNA repair as well as the underlying mechanisms of Cockayne syndrome.
authors: Epigenetics Program, Department of Biochemistry and Biophysics, Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Iltaeg
authors: I
authors: Cho
authors: Pei-Fang
authors: PF
authors: Tsai
authors: Robert J
authors: RJ
authors: Lake
authors: Asjad
authors: A
authors: Basheer
authors: Hua-Ying
authors: HY
authors: Fan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D003057:Cockayne Syndrome / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics; D056488:Histone Chaperones / Q000235:genetics; D006801:Humans; D014158:Transcription, Genetic
chemical_list: D056488:Histone Chaperones; D000255:Adenosine Triphosphate; D004265:DNA Helicases; D045643:DNA Repair Enzymes
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