Microtubules do not promote mitotic slippage when the spindle assembly checkpoint cannot be satisfied

• Main Authors: Brito, Daniela A, Yang, Zhenye, Rieder, Conly L
• Format: Journal Article
• Language: English
• Published: Rockefeller University Press 18.08.2008

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. This research was supported by The National Institutes of Health (GMS40198 to C.L. Rieder) and a doctoral research fellowship (SFRH/BD/13663/2003) from Fundacao para a Ciencia e a Tecnologia (toD.A. Brito). © 2008 Brito et al. This article is distributed under the terms of the Creative Commons Attribution 3.0 License. The definitive version was published in Journal of Cell Biology 182 (2009): 623-629, doi:10.1083/jcb.200805072.