title: UV radiation-induced XPC translocation within chromatin is mediated by damaged-DNA binding protein, DDB2.
abstract: The tumor suppressor p53 protein has been established as an important factor in modulating the efficiency of global genomic repair. Our recent repair studies in human cells reported that p53 regulates the recruitment of XPC and TFIIH proteins to specific DNA damage sites. Here, we have examined the influence of p53 and damaged-DNA binding complex (DDB2) proteins on the distribution of XPC within damaged chromatin in vivo and the recruitment of XPC to DNA damage sites in situ. The results show that UV irradiation causes the translocation of XPC from a loosely bound form into a tight association with chromatin in vivo. The UV radiation-induced redistribution of XPC was equally compromised in p53-deficient, as well as DDB2-deficient, human cells. Similarly, rapid recruitment of XPC to DNA damage in situ was also impaired in both cell lines. Ectopic expression of DDB2 in p53-deficient cells overcame the requirement of p53 function for UV-induced translocation of XPC in vivo. Restoration of DDB2 function also enhanced the recruitment of XPC to DNA damage sites in situ and increased the global repair of cyclobutane pyrimidine dimer from the genome. These results indicate that DDB2 is a key downstream factor of p53 for regulating the movement of XPC to DNA damage in irradiated cells.
authors.affiliation: Department of Radiology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Qi-En
authors.initials: QE
authors.lastname: Wang
authors.forename: Qianzheng
authors.initials: Q
authors.lastname: Zhu
authors.forename: Gulzar
authors.initials: G
authors.lastname: Wani
authors.forename: Jianming
authors.initials: J
authors.lastname: Chen
authors.forename: Altaf A
authors.initials: AA
authors.lastname: Wani
mesh_terms: D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D021381:Protein Transport; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D002843:Chromatin; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; C086984:XPC protein, human