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Originally published as MBoC in Press, 10.1091/mbc.E08-11-1150 on April 1, 2009

Vol. 20, Issue 10, 2626-2637, May 15, 2009

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Cdc14 Inhibition by the Spindle Assembly Checkpoint Prevents Unscheduled Centrosome Separation in Budding Yeast

Elena Chiroli, Giulia Rancati*,{dagger}, Ilaria Catusi*, Giovanna Lucchini, and Simonetta Piatti

Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, 20126 Milan, Italy

Submitted November 26, 2008; Revised March 12, 2009; Accepted March 20, 2009
Monitoring Editor: Orna Cohen-Fix

The spindle assembly checkpoint (SAC) is an evolutionarily conserved surveillance mechanism that delays anaphase onset and mitotic exit in response to the lack of kinetochore attachment. The target of the SAC is the E3 ubiquitin ligase anaphase-promoting complex (APC) bound to its Cdc20 activator. The Cdc20/APC complex is in turn required for sister chromatid separation and mitotic exit through ubiquitin-mediated proteolysis of securin, thus relieving inhibition of separase that unties sister chromatids. Separase is also involved in the Cdc-fourteen early anaphase release (FEAR) pathway of nucleolar release and activation of the Cdc14 phosphatase, which regulates several microtubule-linked processes at the metaphase/anaphase transition and also drives mitotic exit. Here, we report that the SAC prevents separation of microtubule-organizing centers (spindle pole bodies [SPBs]) when spindle assembly is defective. Under these circumstances, failure of SAC activation causes unscheduled SPB separation, which requires Cdc20/APC, the FEAR pathway, cytoplasmic dynein, and the actin cytoskeleton. We propose that, besides inhibiting sister chromatid separation, the SAC preserves the accurate transmission of chromosomes also by preventing SPBs to migrate far apart until the conditions to assemble a bipolar spindle are satisfied.


This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-11-1150) on April 1, 2009.

* These authors contributed equally to this work.

{dagger} Present address: Stowers Institute for Medical Research, 1000 E. 50th St., Kansas City, MO 64110.

Address correspondence to: Simonetta Piatti (simonetta.piatti{at}unimib.it)

Abbreviations used: APC, anaphase-promoting complex; FEAR, Cdc-fourteen early anaphase release; SAC, spindle assembly checkpoint; SPB, spindle pole body.




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C. C. Chai, E. M. Teh, and F. M. Yeong
Unrestrained Spindle Elongation during Recovery from Spindle Checkpoint Activation in cdc15-2 Cells Results in Mis-Segregation of Chromosomes
Mol. Biol. Cell, July 15, 2010; 21(14): 2384 - 2398.
[Abstract] [Full Text] [PDF]




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