Fission yeast dim1(+) encodes a functionally conserved polypeptide essential for mitosis.
In a screen for second site mutations capable of reducing the restrictive temperature of the fission yeast mutant cdc2-D217N, we have isolated a novel temperature-sensitive mutant, dim1-35. When shifted to restrictive temperature, dim1-35 mutant cells arrest before entry into mitosis or proceed through mitosis in the absence of nuclear division, demonstrating an uncoupling of proper DNA segregation from other cell cycle events. Deletion of dim1 from the Schizosaccharomyces pombe genome produces a lethal G2 arrest phenotype. Lethality is rescued by overexpression of the mouse dim1 homolog, mdim1. Likewise, deletion of the Saccharomyces cerevisiae dim1 homolog, CDH1, is lethal. Both mdim1 and dim1(+) are capable of rescuing lethality in the cdh1::HIS3 mutant. Although dim1-35 displays no striking genetic interactions with various other G2/M or mitotic mutants, dim1-35 cells incubated at restrictive temperature arrest with low histone H1 kinase activity. Morevoer, dim1-35 displays sensitivity to the microtubule destabilizing drug, thiabendazole (TBZ). We conclude that Dim1p plays a fundamental, evolutionarily conserved role as a protein essential for entry into mitosis as well as for chromosome segregation during mitosis. Based on TBZ sensitivity and failed chromosome segregation in dim1-35, we further speculate that Dim1p may play a role in mitotic spindle formation and/or function.
Berry
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Howard Hughes Medical Institute, Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37212, USA.
Gould
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000235:genetics; D002237:Carbohydrate Dehydrogenases; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics*; D002467:Cell Nucleus / Q000502:physiology; D017124:Conserved Sequence; D003470:Culture Media / Q000494:pharmacology; D019926:Cyclin B; D016213:Cyclins / Q000235:genetics; D004271:DNA, Fungal; D005656:Fungal Proteins / Q000235:genetics*; D016195:G2 Phase; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D026901:Membrane Transport Proteins; D051379:Mice; D008870:Microtubules; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D009584:Nitrogen / Q000494:pharmacology; D010455:Peptides / Q000235:genetics*; D011494:Protein Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D012568:Schizosaccharomyces / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D013827:Thiabendazole / Q000494:pharmacology
C094693:CDR1 protein, Candida albicans; D018797:Cell Cycle Proteins; D003470:Culture Media; D019926:Cyclin B; D016213:Cyclins; D004271:DNA, Fungal; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D010455:Peptides; D029702:Schizosaccharomyces pombe Proteins; C118369:dim1 protein, S pombe; D002237:Carbohydrate Dehydrogenases; C019859:cellobiose-quinone oxidoreductase; D011494:Protein Kinases; C102333:histone H1 kinase; D016203:CDC2 Protein Kinase; D013827:Thiabendazole; D009584:Nitrogen