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

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 c...

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Autores principales: Gay, Guillaume, Courtheoux, Thibault, Reyes, Céline, Tournier, Sylvie, Gachet, Yannick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308688/
https://www.ncbi.nlm.nih.gov/pubmed/22412019
http://dx.doi.org/10.1083/jcb.201107124
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author Gay, Guillaume
Courtheoux, Thibault
Reyes, Céline
Tournier, Sylvie
Gachet, Yannick
author_facet Gay, Guillaume
Courtheoux, Thibault
Reyes, Céline
Tournier, Sylvie
Gachet, Yannick
author_sort Gay, Guillaume
collection PubMed
description 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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spelling pubmed-33086882012-09-19 A stochastic model of kinetochore–microtubule attachment accurately describes fission yeast chromosome segregation Gay, Guillaume Courtheoux, Thibault Reyes, Céline Tournier, Sylvie Gachet, Yannick J Cell Biol Research Articles 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. The Rockefeller University Press 2012-03-19 /pmc/articles/PMC3308688/ /pubmed/22412019 http://dx.doi.org/10.1083/jcb.201107124 Text en © 2012 Gay et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Gay, Guillaume
Courtheoux, Thibault
Reyes, Céline
Tournier, Sylvie
Gachet, Yannick
A stochastic model of kinetochore–microtubule attachment accurately describes fission yeast chromosome segregation
title A stochastic model of kinetochore–microtubule attachment accurately describes fission yeast chromosome segregation
title_full A stochastic model of kinetochore–microtubule attachment accurately describes fission yeast chromosome segregation
title_fullStr A stochastic model of kinetochore–microtubule attachment accurately describes fission yeast chromosome segregation
title_full_unstemmed A stochastic model of kinetochore–microtubule attachment accurately describes fission yeast chromosome segregation
title_short A stochastic model of kinetochore–microtubule attachment accurately describes fission yeast chromosome segregation
title_sort stochastic model of kinetochore–microtubule attachment accurately describes fission yeast chromosome segregation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308688/
https://www.ncbi.nlm.nih.gov/pubmed/22412019
http://dx.doi.org/10.1083/jcb.201107124
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