title: The role of Cdc55 in the spindle checkpoint is through regulation of mitotic exit in Saccharomyces cerevisiae.
abstract: Cdc55, a B-type regulatory subunit of protein phosphatase 2A, has been implicated in mitotic spindle checkpoint activity and maintenance of sister chromatid cohesion during metaphase. The spindle checkpoint is composed of two independent pathways, one leading to inhibition of the metaphase-to-anaphase transition by checkpoint proteins, including Mad2, and the other to inhibition of mitotic exit by Bub2. We show that Cdc55 is a negative regulator of mitotic exit. A cdc55 mutant, like a bub2 mutant, prematurely releases Cdc14 phosphatase from the nucleolus during spindle checkpoint activation, and premature exit from mitosis indirectly leads to loss of sister chromatid cohesion and inviability in nocodazole. The role of Cdc55 is separable from Bub2 and inhibits release of Cdc14 through a mechanism independent of the known negative regulators of mitotic exit. Epistasis experiments indicate Cdc55 acts either downstream or independent of the mitotic exit network kinase Cdc15. Interestingly, the B-type cyclin Clb2 is partially stable during premature activation of mitotic exit in a cdc55 mutant, indicating mitotic exit is incomplete.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Medical Center, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Yellman
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Burke
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002466:Cell Nucleolus / Q000378:metabolism; D020090:Chromosome Segregation / Q000502:physiology; D004843:Epistasis, Genetic; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D064249:Securin; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: C070351:BUB2 protein, S cerevisiae; C074860:CDC14 protein, S cerevisiae; C071246:CDC55 protein, S cerevisiae; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; C089357:LTE1 protein, S cerevisiae; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C578004:PDS1 protein, S cerevisiae; C416648:SPO12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; C437104:Slk19 protein, S cerevisiae; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases