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Published online August 18, 2008
doi:10.1083/jcb.200805072
The Journal of Cell Biology, Vol. 182, No. 4, 623-629
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Brito et al.
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Microtubules do not promote mitotic slippage when the spindle assembly checkpoint cannot be satisfied



Daniela A. Brito1, Zhenye Yang2, and Conly L. Rieder1,2,3

1 Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, NY 12222
2 Laboratory of Cell Regulation, Division of Molecular Medicine, Wadsworth Center, New York State Department of Health, Albany, NY 12201
3 Marine Biology Laboratory, Woods Hole, MA 02543

Correspondence to Conly L. Rieder: Rieder{at}Wadsworth.org

When the spindle assembly checkpoint (SAC) cannot be satisfied, cells exit mitosis via mitotic slippage. In microtubule (MT) poisons, slippage requires cyclin B proteolysis, and it appears to be accelerated in drug concentrations that allow some MT assembly. To determine if MTs accelerate slippage, we followed mitosis in human RPE-1 cells exposed to various spindle poisons. At 37°C, the duration of mitosis in nocodazole, colcemid, or vinblastine concentrations that inhibit MT assembly varied from 20 to 30 h, revealing that different MT poisons differentially depress the cyclin B destruction rate during slippage. The duration of mitosis in Eg5 inhibitors, which induce monopolar spindles without disrupting MT dynamics, was the same as in cells lacking MTs. Thus, in the presence of numerous unattached kinetochores, MTs do not accelerate slippage. Finally, compared with cells lacking MTs, exit from mitosis is accelerated over a range of spindle poison concentrations that allow MT assembly because the SAC becomes satisfied on abnormal spindles and not because slippage is accelerated.

D.A. Brito and Z. Yang contributed equally to this paper.

Abbreviations used in this paper: APC, anaphase-promoting complex; MT, microtubule; NEB, nuclear envelope breakdown; SAC, spindle assembly checkpoint.

© 2008 Brito et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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