The Gcn2 kinase as a cell cycle regulator.

Cell cycle progression through G1 phase is of particular importance because this is the phase where the decision to embark on another cell cycle is made. An aberrant G1/S transition often leads to cell cycle deregulation and cancer development. Therefore, there is a complex regulatory network to ensure timely entry into S phase, coordinating initiation of DNA replication with growth and stress signals. We have studied the response of fission yeast cells to ultraviolet (UV) irradiation in G1 phase and identified a Gcn2-dependent checkpoint that delays entry into S phase. UV irradiation activates Gcn2 which, in turn, phosphorylates the translation initiation factor eIF2alpha and depresses translation. Phosphorylation of eIF2alpha is a well-known response to various forms of stress, but whether or how this response is causing the specific cell cycle effects is not known. Here we discuss the relationships between Gcn2 activity, eIF2alpha phosphorylation, translation downregulation and cell cycle delay.