title: Reciprocally regulated chromatin association of Cockayne syndrome protein B and p53 protein.
abstract: The Cockayne syndrome complementation group B (CSB) protein is an ATP-dependent chromatin remodeler with an essential function in transcription-coupled DNA repair, and mutations in the CSB gene are associated with Cockayne syndrome. The p53 tumor suppressor has been known to interact with CSB, and both proteins have been implicated in overlapping biological processes, such as DNA repair and aging. The significance of the interaction between CSB and p53 has remained unclear, however. Here, we show that the chromatin association of CSB and p53 is inversely related. Using in vitro binding and chromatin immunoprecipitation approaches, we demonstrate that CSB facilitates the sequence-independent association of p53 with chromatin when p53 concentrations are low and that this is achieved by the interaction of CSB with the C-terminal region of p53. Remarkably, p53 prevents CSB from binding to nucleosomes when p53 concentrations are elevated. Examining the enzymatic properties of CSB revealed that p53 excludes CSB from nucleosomes by occluding a nucleosome interaction surface on CSB. Together, our results suggest that the reciprocal regulation of chromatin access by CSB and p53 could be part of a mechanism by which these two proteins coordinate their activities to regulate DNA repair, cell survival, and aging.
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6145, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lake
authors.forename: Asjad
authors.initials: A
authors.lastname: Basheer
authors.forename: Hua-Ying
authors.initials: HY
authors.lastname: Fan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis; D002470:Cell Survival; D016922:Cellular Senescence; D002843:Chromatin / Q000378:metabolism; D003057:Cockayne Syndrome / Q000235:genetics; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D016678:Genome; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D009707:Nucleosomes / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D002843:Chromatin; D009707:Nucleosomes; D000075223:Poly-ADP-Ribose Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000255:Adenosine Triphosphate; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes