Requirement for tyrosine phosphorylation of Cdk4 in Gl arrest induced by ultraviolet irradiation

EXPOSURE to ultraviolet light arrests the function of mammalian fibroblasts in the Gl phase of the cell cycle, as well as the S and G2 phases. Although ^p21, an inhibitor of cyclin-dependent kinase (Cdk) that is induced by DNA damage may partly account for the arrest in Gl (ref. 1), the mechanism is little understood. Here we show that tyrosine phosphorylation of Cdk4 is required for this arrest. In rat fibroblast, Cdk4 is tyrosine-phosphorylated during Gl progression, and its dephosphorylation is required for S phase. When cells are ultraviolet-irradiated, their arrest in Gl is accompanied by an increase in phosphorylation level. Conversely, cells expressing unphosphorx la table Cdk4^F17 fail to arrest in Gl, and suffer significantly elevated chromosomal aberrations and cell death.