Mutations in CDC14 result in high sensitivity to cyclin gene dosage in Saccharomyces cerevisiae.
We screened for mutations that resulted in lethality when the G1 cyclin Cln2p was overexpressed throughout the cell cycle in Saccharomyces cerevisiae. Mutations in five complementation groups were found to give this phenotype, and three of the mutated genes were identified as MEC1, NUP170, and CDC14. Mutations in CDC14 may have been recovered in the screen because Cdc14p may reduce the cyclin B (Clb)-associated Cdc28 kinase activity in late mitosis, and Cln2p may normally activate Clb-Cdc28 kinase activity by related mechanisms. In agreement with the idea that cdc14 mutations elevate Clb-Cdc28 kinase activity, deletion of the gene for the Clb-Cdc28 inhibitor Sic1 caused synthetic lethality with cdc14-1, as did the deletion of HCT1, which is required for proteolysis of Clb2p. Surprisingly, deletion of the gene for the major B-type cyclin, CLB2, also caused synthetic lethality with the cdc14-1 mutation. The clb2 cdc14 strains arrested with replicated but unseparated DNA and unseparated spindle pole bodies; this phenotype is distinct from the late mitotic arrest of the sic1::TRP1 cdc14-1 and the cdc14-1 hct1::LEU2 double mutants and of the cdc14 CLN2 overexpressor. We found genetic interactions between CDC14 and the replication initiator gene CDC6, extending previous observations of interactions between the late mitotic function of Cdc14p and control of DNA replication. We also describe genetic interactions between CDC28 and CDC14.
Yuste-Rojas
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Rockefeller University, New York, NY 10021, USA.
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D017489:CDC28 Protein Kinase, S cerevisiae / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D016213:Cyclins / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics*; D018628:Gene Dosage; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D008938:Mitosis / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
C074860:CDC14 protein, S cerevisiae; C082721:CLN2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D016213:Cyclins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D017489:CDC28 Protein Kinase, S cerevisiae; D017027:Protein Tyrosine Phosphatases