ULTRAVIOLET-B IRRADIATION-INDUCED G2 CELL-CYCLE ARREST IN HUMAN KERATINOCYTES BY INHIBITORY PHOSPHORYLATION OF THE CDC2 CELL-CYCLE KINASE

In response to genotoxic stress, cell cycle progression can be arreste d at certain checkpoints which serve to maintain genomic integrity. We have investigated the mechanism of ultraviolet B (UVB) irradiation-in duced cell cycle arrest in normal human keratinocytes and in the HaCaT keratinocyte cell line which carries mutant p53 tumour suppressor pro tein. While only normal keratinocytes showed a delay in G1 following s ublethal UVB irradiation both cell types exhibited prolonged G2 arrest attributable to rapid inhibition of cyclin B-associated cdc2 kinase a ctivity. This inhibition coincided with increased tyrosine phosphoryla tion of cdc2 and was reversed by the cdc25C phosphatase in vitro. The data indicate that WE-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.