PREMATURE INITIATION OF MITOSIS IN YEAST LACKING RCC1 OR AN INTERACTING GTPASE

A fission yeast mutant is described in which the onset of mitosis is uncoupled from the completion of DNA replication. pim1 (premature initiation of mitosis) cells can undergo mitotic chromosome condensation and mitotic spindle formation without completion of S phase and without the cdc25 mitotic inducer. The M phase kinase is required for pim1-induced mitosis and becomes activated. pim1 encodes a homolog of the human RCC1 nuclear protein. pim1 mutants are fully rescued by overexpression of spi1, a newly identified essential gene whose predicted product shares 81% identity with human TC4. spi1 and TC4 define a new subclass within the "ras-like" GTPase superfamily that is structurally distinct from the ras, rho, or sec4 families. Diploid yeast that carry one wild-type and one disrupted copy of spi1 have multiple satellite nuclei, and mitotic haploidization occurs at very high frequency. spi1 appears to interact with pim1 in the maintenance of a coordinated cell cycle.