Dominant mutant alleles of yeast protein kinase gene CDC15 suppress the lte1 defect in termination of M phase and genetically interact with CDC14.
LTE1 encodes a homolog of GDP-GTP exchange factors for the Ras superfamily and is required at low temperatures for cell cycle progression at the stage of the termination of M phase in Saccharomyces cerevisiae. We isolated extragenic suppressors which suppress the cold sensitivity of lte1 cells and confer a temperature-sensitive phenotype on cells. Cells mutant for the suppressor alone were arrested at telophase at non-permissive temperatures and the terminal phenotype was almost identical to that of lte1 cells at non-permissive temperatures. Genetic analysis revealed that the suppressor is allelic to CDC15, which encodes a protein kinase. The cdc15 mutations thus isolated were recessive with regard to the temperature-sensitive phenotype and were dominant with respect to suppression of lte1. We isolated CDC14 as a low-copy-number suppressor of cdc15-rlt1. CDC14 encodes a phosphotyrosine phosphatase (PTPase) and is essential for termination of M phase. An extra copy of CDC14 suppressed the temperature sensitivity of cdc15-rlt1 cells, but not that of cdc15-1 cells. In addition, some residues that are essential for the CDC14 PTPase activity were found to be non-essential for the suppression. These results strongly indicate that Cdc14 possesses dual functions; PTPase activity is needed for one function but not for the other. We postulate that the cooperative action of Cdc14 and Cdc15 plays an essential role in the termination of M phase.
Shirayama
M
M
Department of Biological Sciences, Graduate School of Science, University of Tokyo, Japan.
Matsui
Y
Y
Toh-e
A
A
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics*; D017931:DNA Primers; D005656:Fungal Proteins / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D005799:Genes, Dominant; D020662:Guanine Nucleotide Exchange Factors; D008938:Mitosis / Q000235:genetics*; D008969:Molecular Sequence Data; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013489:Suppression, Genetic
C074860:CDC14 protein, S cerevisiae; C082279:CDC15 protein; D018797:Cell Cycle Proteins; D017931:DNA Primers; D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; C089357:LTE1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D017027:Protein Tyrosine Phosphatases; D019204:GTP-Binding Proteins