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Tension can directly suppress Aurora B kinase-triggered release of kinetochore-microtubule attachments

Chromosome segregation requires sister kinetochores to attach microtubules emanating from opposite spindle poles. Proper attachments come under tension and are stabilized, but defective attachments lacking tension are released, giving another chance for correct attachments to form. This error correc...

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Autores principales: de Regt, Anna K., Clark, Cordell J., Asbury, Charles L., Biggins, Sue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021268/
https://www.ncbi.nlm.nih.gov/pubmed/35443757
http://dx.doi.org/10.1038/s41467-022-29542-8
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author de Regt, Anna K.
Clark, Cordell J.
Asbury, Charles L.
Biggins, Sue
author_facet de Regt, Anna K.
Clark, Cordell J.
Asbury, Charles L.
Biggins, Sue
author_sort de Regt, Anna K.
collection PubMed
description Chromosome segregation requires sister kinetochores to attach microtubules emanating from opposite spindle poles. Proper attachments come under tension and are stabilized, but defective attachments lacking tension are released, giving another chance for correct attachments to form. This error correction process depends on Aurora B kinase, which phosphorylates kinetochores to destabilize their microtubule attachments. However, the mechanism by which Aurora B distinguishes tense versus relaxed kinetochores remains unclear because it is difficult to detect kinase-triggered detachment and to manipulate kinetochore tension in vivo. To address these challenges, we apply an optical trapping-based assay using soluble Aurora B and reconstituted kinetochore-microtubule attachments. Strikingly, the tension on these attachments suppresses their Aurora B-triggered release, suggesting that tension-dependent changes in the conformation of kinetochores can regulate Aurora B activity or its outcome. Our work uncovers the basis for a key mechano-regulatory event that ensures accurate segregation and may inform studies of other mechanically regulated enzymes.
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spelling pubmed-90212682022-04-28 Tension can directly suppress Aurora B kinase-triggered release of kinetochore-microtubule attachments de Regt, Anna K. Clark, Cordell J. Asbury, Charles L. Biggins, Sue Nat Commun Article Chromosome segregation requires sister kinetochores to attach microtubules emanating from opposite spindle poles. Proper attachments come under tension and are stabilized, but defective attachments lacking tension are released, giving another chance for correct attachments to form. This error correction process depends on Aurora B kinase, which phosphorylates kinetochores to destabilize their microtubule attachments. However, the mechanism by which Aurora B distinguishes tense versus relaxed kinetochores remains unclear because it is difficult to detect kinase-triggered detachment and to manipulate kinetochore tension in vivo. To address these challenges, we apply an optical trapping-based assay using soluble Aurora B and reconstituted kinetochore-microtubule attachments. Strikingly, the tension on these attachments suppresses their Aurora B-triggered release, suggesting that tension-dependent changes in the conformation of kinetochores can regulate Aurora B activity or its outcome. Our work uncovers the basis for a key mechano-regulatory event that ensures accurate segregation and may inform studies of other mechanically regulated enzymes. Nature Publishing Group UK 2022-04-20 /pmc/articles/PMC9021268/ /pubmed/35443757 http://dx.doi.org/10.1038/s41467-022-29542-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
de Regt, Anna K.
Clark, Cordell J.
Asbury, Charles L.
Biggins, Sue
Tension can directly suppress Aurora B kinase-triggered release of kinetochore-microtubule attachments
title Tension can directly suppress Aurora B kinase-triggered release of kinetochore-microtubule attachments
title_full Tension can directly suppress Aurora B kinase-triggered release of kinetochore-microtubule attachments
title_fullStr Tension can directly suppress Aurora B kinase-triggered release of kinetochore-microtubule attachments
title_full_unstemmed Tension can directly suppress Aurora B kinase-triggered release of kinetochore-microtubule attachments
title_short Tension can directly suppress Aurora B kinase-triggered release of kinetochore-microtubule attachments
title_sort tension can directly suppress aurora b kinase-triggered release of kinetochore-microtubule attachments
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021268/
https://www.ncbi.nlm.nih.gov/pubmed/35443757
http://dx.doi.org/10.1038/s41467-022-29542-8
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