FISSION YEAST STE9, A HOMOLOG OF HCT1 CDH1 AND FIZZY-RELATED, IS A NOVEL NEGATIVE REGULATOR OF CELL-CYCLE PROGRESSION DURING G(1)-PHASE/

When proliferating fission yeast cells are exposed to nitrogen starvat ion, they initiate conjugation and differentiate into ascospores. Cell cycle arrest in the G(1)-phase is one of the prerequisites for cell d ifferentiation, because conjugation occurs only in the pre-Start G(1)- phase. The role of ste9(+) in the cell cycle progression was investiga ted. Ste9 is a WD-repeat protein that is highly homologous to Hct1/Cdh 1 and Fizzy-related. The ste9 mutants were sterile because they were d efective in cell cycle arrest in the G(1)-phase upon starvation. Steri lity was partially suppressed by the mutation in cig2 that encoded the major G(1)/S cyclin. Although cells lacking Ste9 function grow normal ly, the ste9 mutation was synthetically lethal with the wee1 mutation. In the double mutants of ste9 cdC10(ts), cells arrested in G(1)-phase at the restrictive temperature, but the level of mitotic cyclin (Cdc1 3) did not decrease. In these cells, abortive mitosis occurred from th e pre-Start G(1)-phase. Overexpression of Ste9 decreased the Cdc13 pro tein level and the H1-histone kinase activity. In these cells, mitosis was inhibited and an extra round of DNA replication occurred. Ste9 re gulates G(1) progression possibly by controlling the amount of the mit otic cyclin in the G(1)-phase.