P65(CDC18) PLAYS A MAJOR ROLE CONTROLLING THE INITIATION OF DNA-REPLICATION IN FISSION YEAST

A key problem in the cell cycle is understanding what brings about the initiation of DNA replication and how this is linked with global cell cycle controls. The fission yeast gene cdc18 is required for DNA repl ication and is transcriptionally activated by the cdc10/res1/res2 cont rol acting at START in late G1. We show here that overexpressing cdc18 is able to bring about repeated rounds of DNA synthesis in the absenc e of mitosis and of continuing protein synthesis. The level of the cdc 18-encoded protein p65(cdc18) is periodic in the cell cycle, peaking a t the G1 to S phase transition, and p65(cdc18) is located in the nucle us when cdc18 is overexpressed. We propose that p65(cdc18) acts af the initiation of DNA replication and plays a major role in controlling t he onset of S phase.