title: A stochastic model of kinetochore-microtubule attachment accurately describes fission yeast chromosome segregation.
abstract: 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.
authors.affiliation: Laboratoire de biologie cellulaire et moléculaire du contrôle de la proliferation, Université de Toulouse, F-31062 Toulouse, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gay
authors.forename: Thibault
authors.initials: T
authors.lastname: Courtheoux
authors.forename: Céline
authors.initials: C
authors.lastname: Reyes
authors.forename: Sylvie
authors.initials: S
authors.lastname: Tournier
authors.forename: Yannick
authors.initials: Y
authors.lastname: Gachet
mesh_terms: D064127:Aurora Kinases; D002842:Chromatids / Q000378:metabolism; D020090:Chromosome Segregation / Q000502:physiology*; D015825:Chromosomes, Fungal / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism* / Q000648:ultrastructure; D013269:Stochastic Processes
chemical_list: D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases