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Mol Syst Biol

Title:		Analysis of the mitotic exit control system using locked levels of stable mitotic cyclin
Author(s):		Drapkin BJ; Lu Y; Procko AL; Timney BL; Cross FR;
Address:		"Laboratory of Yeast Molecular Genetics, The Rockefeller University, New York, NY 10021, USA"
Journal Title:		Mol Syst Biol
Year:		2009
Volume:		20091117
Issue:
Page Number:		328 -
DOI:		10.1038/msb.2009.78
ISSN/ISBN:		1744-4292 (Electronic) 1744-4292 (Linking)
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"
Keywords:		"Active Transport, Cell Nucleus/drug effects Anaphase/drug effects Biosensing Techniques Cell Nucleolus/drug effects/metabolism Cyclin B/*metabolism G1 Phase/drug effects Histones/metabolism Mating Factor *Mitosis/drug effects Models, Genetic Peptides/phar;"
Notes:		"MedlineDrapkin, Benjamin J Lu, Ying Procko, Andrea L Timney, Benjamin L Cross, Frederick R eng R01 GM078989/GM/NIGMS NIH HHS/ R01 GM079207/GM/NIGMS NIH HHS/ R01 GM079207-03/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural England 2009/11/19 Mol Syst Biol. 2009; 5:328. doi: 10.1038/msb.2009.78. Epub 2009 Nov 17"