期刊
JOURNAL OF CELL BIOLOGY
卷 196, 期 6, 页码 757-774出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201107124
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资金
- Centre National de la Recherche Scientifique
- L'Agence Nationale de la Recherche [blanc 120601]
- La ligue contre le cancer
- Association pour lo Recherche sur le Cancer
- l'Association de la Recherche sum le Cancer
- GlaxoSmithKline
In fission yeast, erroneous attachments of spindle microtubules to kinetochores are frequent in early mitosis. Most are corrected before anaphase onset by a mechanism involving the protein kinase Aurora B, which destabilizes kinetochore microtubules (ktMTs) in the absence of tension between sister chromatids. In this paper, we describe a minimal mathematical model of fission yeast chromosome segregation based on the stochastic attachment and detachment of ktMTs. The model accurately reproduces the timing of correct chromosome biorientation and segregation seen in fission yeast. Prevention of attachment defects requires both appropriate kinetochore orientation and an Aurora B like activity. The model also reproduces abnormal chromosome segregation behavior (caused by, for example, inhibition of Aurora B). It predicts that, in metaphase, merotelic attachment is prevented by a kinetochore orientation effect and corrected by an Aurora B like activity, whereas in anaphase, it is corrected through unbalanced forces applied to the kinetochore. These unbalanced forces are sufficient to prevent aneuploidy.
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