The p38 mitogen-activated protein kinase augments nucleotide excision repair by mediating DDB2 degradation and chromatin relaxation.
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.
Zhao
Qun
Q
Department of Radiology, The Ohio State University, Columbus, Ohio 43210, USA.
Barakat
Bassant M
BM
Qin
Song
S
Ray
Alo
A
El-Mahdy
Mohamed A
MA
Wani
Gulzar
G
Arafa
El-Shaimaa
el-S
Mir
Safita N
SN
Wang
Qi-En
QE
Wani
Altaf A
AA
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*
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