Nocodazole induces mitotic cell death with apoptotic-like features in Saccharomyces cerevisiae |
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Authors: | Kingo Endo |
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Institution: | Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan |
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Abstract: | We investigated the fate of budding yeast treated with nocodazole, a microtubule-depolymerizing drug. Cells died after mitotic arrest while staying in mitosis, suggesting that mitotic cell death, but not mitotic slippage, mainly occurs in nocodazole-treated cells. Nocodazole-treated cells showed features of apoptotic-like cell death, but not those of cell lysis or autophagy. Consistently, mitochondria-dependent production of reactive oxygen species was involved in the cell death. Similar cell death was also seen in cells after mitotic arrest by perturbation of the anaphase-promoting complex/cyclosome. In addition, caspase activity was found in nocodazole-treated cells, which was independent of the metacaspase, Mca1. Our results suggest that budding yeast can be a model to study mitotic cell death in cancer treatment with antimitotic drugs. |
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Keywords: | ROS reactive oxygen species APC/C anaphase-promoting complex/cyclosome SAC spindle assembly checkpoint PI propidium iodide TUNEL terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling GFP green fluorescent protein |
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