COUPLING OF DNA-REPLICATION AND MITOSIS BY FISSION YEAST RAD4 CUT5/

The fission yeast cut5(+) (identical to rad4(+)) gene is essential for S phase. Its temperature-sensitive (ts) mutation causes mitosis while S phase is inhibited: dependence of mitosis upon the completion of S phase is abolished. If DNA is damaged in mutant cells, however, cell d ivision is arrested. Thus the checkpoint control system for DNA damage is functional, while that for DNA synthesis inhibition is not in the cut5 mutants. Transcription of the cut5(+) gene is not under the direc t control of cdc10(+), which encodes a transcription factor for the ST ART of cell cycle. The transcript level does not change during the cel l cycle. The protein product has four distinct domains and is enriched in the nucleus. Its level does not alter during the cell cycle. The N -domain is important for cut5 protein function: it is essential for co mplementation of ts cut5 mutations and its overexpression blocks cell division. Furthermore, it resembles the N-terminal repeat domain of pr oto-oncoprotein Ect2, which, in the C-domain, contains a regulator-lik e sequence for small G proteins. We discuss a hypothesis that the cut5 protein is an essential component of the checkpoint control system fo r the completion of DNA synthesis. The restraint of mitosis until the completion of S phase is mediated by the cuts' protein, which can sens e the state of chromosome duplication and negatively interacts with M phase regulators such as cdc25 and cdc2.