title: Ultraviolet B irradiation-induced G2 cell cycle arrest in human keratinocytes by inhibitory phosphorylation of the cdc2 cell cycle kinase.
abstract: In response to genotoxic stress, cell cycle progression can be arrested at certain checkpoints which serve to maintain genomic integrity. We have investigated the mechanism of ultraviolet B (UVB) irradiation-induced cell cycle arrest in normal human keratinocytes and in the HaCaT keratinocyte cell line which carries mutant p53 tumour suppressor protein. While only normal keratinocytes showed a delay in G1 following sublethal UVB irradiation both cell types exhibited prolonged G2 arrest attributable to rapid inhibition of cyclin B-associated cdc2 kinase activity. This inhibition coincided with increased tyrosine phosphorylation of cdc2 and was reversed by the cdc25C phosphatase in vitro. The data indicate that UVB-induced G2 arrest in mammalian cells is mediated by inhibitory tyrosine phosphorylation of cdc2 and acts as a defense mechanism against DNA damage irrespective of the cells' p53 status.
mesh_terms: D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000528:radiation effects*; D002453:Cell Cycle / Q000528:radiation effects; D002478:Cells, Cultured; D016213:Cyclins / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D016195:G2 Phase / Q000528:radiation effects*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology / Q000528:radiation effects*; D009154:Mutation; D010766:Phosphorylation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D014443:Tyrosine; D016203:CDC2 Protein Kinase