Mutant casein kinase I (Hrr25p/Kti14p) abrogates the G1 cell cycle arrest induced by Kluyveromyces lactiszymocin in budding yeast.
Zymocin, a toxic protein complex produced by Kluyveromyces lactis, inhibits cell cycle progression in Saccharomyces cerevisiae. In studying its action, a resistant mutant ( kti14-1) was found to express the tot-phenotype typical of totDelta cells, toxin target (TOT) mutants that are impaired in RNA polymerase II Elongator function. Phenotypic analysis of a kti14-1 tot3Delta double mutant revealed a functional link between KTI14 and TOT/Elongator. Unlike totDelta cells, the kti14-1 mutant is sensitive to the drug methylmethane sulfonate (MMS), indicating that, besides being affected in TOT function, kti14-1 cells are also compromised in DNA repair. Single-copy complementation identified HRR25, which codes for casein kinase I (CKI), as KTI14. Kinase-minus hrr25 mutations (K38A and T176I) conferred zymocin resistance, while deletion of the other yeast CKI genes ( YCK1-3) had no effect. A mutation in KTI14 that truncates the P/Q-rich C-terminus of Hrr25p also dissociates MMS sensitivity from zymocin resistance; this mutant is resistant to the toxin, but shows normal sensitivity to MMS. Thus, although kinase-minus mutations are sufficient to protect yeast cells from zymocin, toxicity is also dependent on the integrity of the C-terminal region of Hrr25p, which has been implicated in determining the substrate specificity or localization of Hrr25p.
Mehlgarten
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Biologicum, Institut für Genetik, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 10, Germany.
Schaffrath
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D000483:Alleles; D047389:Casein Kinase I; D047388:Casein Kinases; D002453:Cell Cycle; D016193:G1 Phase; D005816:Genetic Complementation Test; D007716:Kluyveromyces / Q000235:genetics*; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008957:Models, Genetic; D009154:Mutation; D016366:Open Reading Frames; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D004718:Saccharomycetales / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors
D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate; D011494:Protein Kinases; D047389:Casein Kinase I; D047388:Casein Kinases; C070775:HRR25 protein, S cerevisiae; C479664:YCK1 protein, S cerevisiae