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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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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. |
format | Online Article Text |
id | pubmed-9021268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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