Molecular Genetics and Genomics

, Volume 270, Issue 2, pp 156–164

A novel yeast mutant that is defective in regulation of the Anaphase-Promoting Complex by the spindle damage checkpoint

Original Paper

DOI: 10.1007/s00438-003-0912-5

Cite this article as:
Lai, L.A., Morabito, L. & Holloway, S.L. Mol Genet Genomics (2003) 270: 156. doi:10.1007/s00438-003-0912-5

Abstract

The accurate segregation of sister chromatids at the metaphase to anaphase transition in Saccharomyces cerevisiae is regulated by the activity of the anaphase-promoting complex or cyclosome (APC/C). In the event of spindle damage or monopolar spindle attachment, the spindle checkpoint is activated and inhibits APC/C activity towards the anaphase inhibitor Pds1p, resulting in a cell cycle arrest at metaphase. We have identified a novel allele of a gene for an APC/C subunit, cdc16-183 , in S. cerevisiae. cdc16-183 mutants arrest at metaphase at 37°C, and are supersensitive to the spindle-damaging agent nocodazole, which activates the spindle checkpoint, at lower temperatures. This supersensitivity to nocodazole cannot be explained by impairment of the spindle checkpoint pathway, as cells respond normally to spindle damage with a stable metaphase arrest and high levels of Pds1p. Despite showing metaphase arrest at G2/M at 37°C, cdc16-183 mutants are able to perform tested G1 functions normally at this temperature. This is the first demonstration that a mutation in a core APC/C subunit can result in a MAD2-dependent arrest at the restrictive temperature. Our results suggest that the cdc16-183 mutant may have a novel APC/C defect(s) that mimics or activates the spindle checkpoint pathway.

Keywords

Mitosis Saccharomyces cerevisiaeSpindle checkpoint CDC16Anaphase-promoting complex (APC/C)

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiophysicsUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Howard Hughes Medical InstituteUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of GeneticsUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Signal Transduction ProgramThe Burnham InstituteLa JollaUSA