title: Suppression of the Schizosaccharomyces pombe cut12.1 cell-cycle defect by mutations in cdc25 and genes involved in transcriptional and translational control.
abstract: Cdc25 phosphatase primes entry to mitosis by removing the inhibitory phosphate that is transferred to mitosis promoting factor (MPF) by Wee1 related kinases. A positive feedback loop then boosts Cdc25 and represses Wee1 activities to drive full-scale MPF activation and commitment to mitosis. Dominant mutations in the Schizosaccharomyces pombe spindle pole body (SPB) component Cut12 enable cdc25.22 mutants to overcome a G2 arrest at 36 degrees and enter mitosis. The recessive temperature-sensitive cut12.1 mutation results in the formation of monopolar spindles in which the spindle pole marker Sad1 is enriched on the nonfunctional SPB at 36 degrees . We identified mutations at five loci that suppressed the lethality of the recessive cut12.1 mutation at 36 degrees and conferred lethality at 20 degrees . Three of the five mutations led to the formation of monopolar spindles at restrictive temperatures, affected cell size at commitment to mitosis, and generated multiple Sad1 foci at nuclear periphery. The five loci, tfb2.rt1, tfb5.rt5, pla1.rt3, rpl4301.rt4, and rot2.1, and multicopy suppressors, including tfb1(+) and dbp10(+), are involved in transcription, translation, or RNA processing, prompting us to establish that elevating Cdc25 levels with the dominant cdc25.d1 allele, suppressed cut12.1. Thus, rot mutants provide a further link between protein production and cell-cycle progression.
authors.affiliation: CRUK Cell Division Group, Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, United Kingdom.
authors.forename: Victor A
authors.initials: VA
authors.lastname: Tallada
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Bridge
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Emery
authors.forename: Iain M
authors.initials: IM
authors.lastname: Hagan
mesh_terms: D002453:Cell Cycle; D003001:Cloning, Molecular; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D050505:Mutant Proteins / Q000302:isolation & purification; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D013489:Suppression, Genetic; D014158:Transcription, Genetic; D020687:cdc25 Phosphatases / Q000235:genetics
chemical_list: C111708:Cut12 protein, S pombe; D008869:Microtubule-Associated Proteins; D050505:Mutant Proteins; D010750:Phosphoproteins; D029702:Schizosaccharomyces pombe Proteins; D020687:cdc25 Phosphatases