THE IDENTIFICATION OF CDNAS THAT AFFECT THE MITOSIS-TO-INTERPHASE TRANSITION IN SCHIZOSACCHAROMYCES-POMBE, INCLUDING SBP1, WHICH ENCODES A SPI1P-GTP-BINDING PROTEIN

Perturbations of the spilp GTPase system in fission yeast, caused by m utation or overexpression of several regulatory proteins, result in a unique terminal phenotype that includes condensed chromosomes, a nide medial septum, and a fragmented nuclear envelope. To identify potentia l regulators or targets of the spilp GTPase system, a screen for cDNAs whose overexpression results in this terminal phenotype was conducted , and seven clones that represent three genes, named med1, med2, and m ed3 (mitotic exit defect), were identified. Their genetic interaction with the spi1p GTPase system was established by showing that the spilp guanine nucleotide exchange factor mutant pim1-d1(ts) was hypersensit ive to their overexpression. med1 encodes a homologue of the human Ran -binding protein, RanBP1, and has been renamed sbp1 (spi1-binding prot ein). sbp1p binds to spi1p-GTP and costimulates the GTPase-activating protein (GAP)-catalyzed GTPase activity. Cells in which sbp1p is deple ted or overproduced phenocopy cells in which the balance between spi1p -GTP and spi1p-GDP is perturbed by other means. Therefore, sbp1p media tes and/or regulates the essential functions of the spi1p GTPase syste m. med2 and med3 encode novel fission yeast proteins that, based on ou r phenotypic analyses, are likely to identify additional regulators or effecters of the spilp GTPase system.