The Cdk inhibitors p25(rum1) and p40(SIC1) are functional homologues that play similar roles in the regulation of the cell cycle in fission and budding yeast

摘要

p25(rum1) and p40(SIC1) are specific inhibitors of p34(cdc2/CDC28) kinase complexes with B-type cyclins that play a central role in the regulation of the G(1) phase of the cell cycle. We show here that low levels of expression of SIC1 in Schizosaccharomyces pombe rescues all the phenotypes of cells lacking the rum1(+) gene. In addition, high level expression of SIC1 in S. pombe induces extra rounds of DNA replication without mitosis, a phenotype very similar to the overexpression of rum1(+). Transient expression of rum1(+) in S. cerevisiae restores the G(1) arrest phenotype of cdc4 sic1 Delta double mutants. Overproduction of rum1(+) in Saccharomyces cerevisiae causes a cell cycle block in G(1) with a phenotype similar to inactivation of all the Clb cyclins. Finally, we have mapped the cyclin interacting domain and Cdk inhibitory domain to a region of about 80 amino acids in p25(rum1) that has significant homology to the C-terminal domain of p40(SIC1). All these observations suggest that fission yeast p25(rum1) and budding yeast p40(SIC1) define a family of Cdk inhibitors that specifically down regulate cyclin B/Cdk1 during the G(1) phase of the cell cycle. [References: 55]