Reference: Toda K, et al. (2012) APC/C-Cdh1-dependent anaphase and telophase progression during mitotic slippage. Cell Div 7(1):4

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Abstract

ABSTRACT: BACKGROUND: The spindle assembly checkpoint (SAC) inhibits anaphase progression in the presence of insufficient kinetochore-microtubule attachments, but cells can eventually escape from this mitotic arrest by a process known as called mitotic slippage or adaptation. This is a problem for cancer chemotherapy using microtubule poisons. RESULTS: Here we describe mitotic slippage in budding yeast. Precocious activation of anaphase promoting complex/cyclosome (APC/C)-Cdh1 caused mitotic slippage in the presence of nocodazole, while SAC was still active. APC/C-Cdh1, but not APC/C-Cdc20, triggered anaphase progression (securin degradation, separase-mediated cohesin cleavage and sister-chromatid separation), in addition to telophase onset (mitotic exit), during mitotic slippage. This demonstrates that an inhibitory system not only of APC/C-Cdc20 but also of APC/C-Cdh1 is critical for accurate chromosome segregation in the presence of unsatisfied kinetochore-microtubule attachments. CONCLUSIONS: The sequential activation of APC/C-Cdc20-to-APC/C-Cdh1 during mitosis is the heart of accurate mitosis. Precocious activation of APC/C-Cdh1 in metaphase (pre-anaphase) causes mitotic slippage in nocodazole-treated cells. For prevention of mitotic slippage, concomitant inhibition of APC/C-Cdh1 may be effective for tumor therapy with mitotic spindle poisons in human.

Reference Type
Journal Article
Authors
Toda K, Naito K, Mase S, Ueno M, Uritani M, Yamamoto A, Ushimaru T
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