A role for the START gene-specific transcription factor complex in the inactivation of cyclin B and Cut2 destruction.
Hyperactivation of Cdc2 in fission yeast causes cells to undergo a lethal premature mitosis called mitotic catastrophe. This phenotype is observed in cdc2-3w wee1-50 cells at high temperature. Eleven of 17 mutants that suppress this phenotype define a single complementation group, mcs1. The mcs1-77 mutant also suppresses lethal inactivation of the Wee1 and Mik1 tyrosine kinases and thus delays mitosis independently of Cdc2 tyrosine phosphorylation. We have cloned mcs1 by isolating suppressors of the cell cycle arrest phenotype of mcs1-77 cdc25-22 cells and found that it encodes Res2, a component of the START gene-specific transcription factor complex MBF (also known as DSC-1). The mcs1-77 mutant bears a single point mutation in the DNA-binding domain of Res2 that causes glycine 68 to be replaced by a serine residue. Importantly, two substrates of the anaphase-promoting complex (APC), the major B-type cyclin, Cdc13, and the anaphase inhibitor, Cut2, are unstable in G2-phase mcs1-77 cells. Consistent with this, we observe abnormal sister chromatid separation in mcs1-77 cdc25-22 cells at the restrictive temperature. Mutation of either Cdc10 or Res1 also deregulates MBF-dependent transcription and causes a G2 delay. We find that this cell cycle delay is abolished in the absence of the APC regulator Ste9/Srw1 and that the periodic expression of Ste9/Srw1 is controlled by the MBF complex. These data suggest that in fission yeast the MBF complex plays a key role in the inactivation of cyclin B and Cut2 destruction by controlling the periodic production of APC regulators.
Tournier
S
S
Division of Yeast Genetics, National Institute for Medical Research, London, United Kingdom.
Millar
J B
JB
D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D018387:Codon, Initiator / Q000235:genetics*; D019926:Cyclin B / Q000037:antagonists & inhibitors / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase; D015966:Gene Expression Regulation, Fungal; D015698:Genomic Library; D005838:Genotype; D008540:Meiosis; D016254:Mutagenesis, Insertional; D016366:Open Reading Frames; D010641:Phenotype; D016196:S Phase; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics* / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins; D064249:Securin; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000378:metabolism*
D018797:Cell Cycle Proteins; D018387:Codon, Initiator; C103136:Cut2 protein, S pombe; D019926:Cyclin B; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins; D064249:Securin; D014157:Transcription Factors; D016203:CDC2 Protein Kinase