Analysis of the mitotic exit control system using locked levels of stable mitotic cyclin

Benjamin J. Drapkin, Ying Lu, Andrea L. Procko, Benjamin L. Timney, Frederick R. Cross

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Cyclin-dependent kinase (Cdk) both promotes mitotic entry (spindle assembly and anaphase) and inhibits mitotic exit (spindle disassembly and cytokinesis), leading to an elegant quantitative hypothesis that a single cyclin oscillation can function as a ratchet to order these events. This ratchet is at the core of a published ODE model for the yeast cell cycle. However, the ratchet model requires appropriate cyclin dose-response thresholds. Here, we test the inhibition of mitotic exit in budding yeast using graded levels of stable mitotic cyclin (Clb2). In opposition to the ratchet model, stable levels of Clb2 introduced dose-dependent delays, rather than hard thresholds, that varied by mitotic exit event. The ensuing cell cycle was highly abnormal, suggesting a novel reason for cyclin degradation. Cdc14 phosphatase antagonizes Clb2-Cdk, and Cdc14 is released from inhibitory nucleolar sequestration independently of stable Clb2. Thus, Cdc14/Clb2 balance may be the appropriate variable for mitotic regulation. Although our results are inconsistent with the aforementioned ODE model, revision of the model to allow Cdc14/Clb2 balance to control mitotic exit corrects these discrepancies, providing theoretical support for our conclusions.

Original languageEnglish (US)
Article number328
JournalMolecular Systems Biology
Volume5
DOIs
StatePublished - Jan 20 2009

Keywords

  • Cell cycle
  • Cyclin
  • Mathematical model
  • Mitosis
  • Oscillator

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Fingerprint Dive into the research topics of 'Analysis of the mitotic exit control system using locked levels of stable mitotic cyclin'. Together they form a unique fingerprint.

Cite this