A stochastic model of kinetochore-microtubule attachment accurately describes fission yeast chromosome segregation.

Guillaume Gay, Thibault Courtheoux, Céline Reyes, Sylvie Tournier, Yannick Gachet

Laboratoire de biologie cellulaire et moléculaire du contrôle de la proliferation, Université de Toulouse, F-31062 Toulouse, France.

The Journal of cell biology 2012 Mar 19

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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.

Citation

Guillaume Gay, Thibault Courtheoux, Céline Reyes, Sylvie Tournier, Yannick Gachet. A stochastic model of kinetochore-microtubule attachment accurately describes fission yeast chromosome segregation. The Journal of cell biology. 2012 Mar 19;196(6):757-74