Dominant alleles of Saccharomyces cerevisiae CDC20 reveal its role in promoting anaphase

Genetics. 1998 Feb;148(2):599-610. doi: 10.1093/genetics/148.2.599.

Abstract

We identified an allele of Saccharomyces cerevisiae CDC20 that exhibits a spindle-assembly checkpoint defect. Previous studies indicated that loss of CDC20 function caused cell cycle arrest prior to the onset of anaphase. In contrast, CDC20-50 caused inappropriate cell cycle progression through M phase in the absence of mitotic spindle function. This effect of CDC20-50 was dominant over wild type and was eliminated by a second mutation causing loss of function, suggesting that it encodes an overactive form of Cdc20p. Overexpression of CDC20 was found to cause a similar checkpoint defect, causing bypass of the preanaphase arrest produced by either microtubule-depolymerizing compounds or MPS1 overexpression. CDC20 overexpression was also able to overcome the anaphase delay caused by high levels of the anaphase inhibitor Pds1p, but not a mutant form immune to anaphase-promoting complex- (APC-)mediated proteolysis. CDC20 overexpression was unable to promote anaphase in cells deficient in APC function. These findings suggest that Cdc20p is a limiting factor that promotes anaphase entry by antagonizing Pds1p. Cdc20p may promote the APC-dependent proteolytic degradation of Pds1p and other factors that act to inhibit cell cycle progression through mitosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Anaphase / physiology*
  • Cdc20 Proteins
  • Cell Cycle Proteins / genetics*
  • Flow Cytometry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Fungal / genetics
  • Genes, Dominant / genetics*
  • Molecular Sequence Data
  • Mutation / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phenotype
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins*
  • Securin
  • Sequence Homology, Amino Acid

Substances

  • CDC20 protein, S cerevisiae
  • Cdc20 Proteins
  • Cell Cycle Proteins
  • Fungal Proteins
  • Nuclear Proteins
  • PDS1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Securin
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • MPS1 protein, S cerevisiae