title: The p38 mitogen-activated protein kinase augments nucleotide excision repair by mediating DDB2 degradation and chromatin relaxation.
abstract: The p38 MAPK is a family of serine/threonine protein kinases that play important roles in cellular responses to external stress signals, e.g. UV irradiation. To assess the role of p38 MAPK pathway in nucleotide excision repair (NER), the most versatile DNA repair pathway, we determined the efficiency of NER in cells treated with p38 MAPK inhibitor SB203580 and found that p38 MAPK is required for the prompt repair of UV-induced DNA damage CPD. We further investigated the possible mechanism through which p38 MAPK regulates NER and found that p38 MAPK mediates UV-induced histone H3 acetylation and chromatin relaxation. Moreover, p38 MAPK also regulates UV-induced DDB2 ubiquitylation and degradation via phosphorylation of the target protein. Finally, our results showed that p38 MAPK is required for the recruitment of NER factors XPC and TFIIH to UV-induced DNA damage sites. We conclude that p38 MAPK regulates chromatin remodeling as well as DDB2 degradation for facilitating NER factor assembly.
authors.affiliation: Department of Radiology, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhao
authors.forename: Bassant M
authors.initials: BM
authors.lastname: Barakat
authors.forename: Song
authors.initials: S
authors.lastname: Qin
authors.forename: Alo
authors.initials: A
authors.lastname: Ray
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: El-Mahdy
authors.forename: Gulzar
authors.initials: G
authors.lastname: Wani
authors.forename: El-Shaimaa
authors.initials: el-S
authors.lastname: Arafa
authors.forename: Safita N
authors.initials: SN
authors.lastname: Mir
authors.forename: Qi-En
authors.initials: QE
authors.lastname: Wang
authors.forename: Altaf A
authors.initials: AA
authors.lastname: Wani
mesh_terms: D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008954:Models, Biological; D008956:Models, Chemical; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D025801:Ubiquitin / Q000378:metabolism; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D002843:Chromatin; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006657:Histones; D007093:Imidazoles; D011725:Pyridines; D025801:Ubiquitin; C086984:XPC protein, human; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580