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Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis

Aurora B kinase is essential for faithful chromosome segregation during mitosis. During (pro)metaphase, Aurora B is concentrated at the inner centromere by the kinases Haspin and Bub1. However, how Haspin and Bub1 collaborate to control Aurora B activity at centromeres remains unclear. Here, we show...

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Autores principales: Hadders, Michael A., Hindriksen, Sanne, Truong, My Anh, Mhaskar, Aditya N., Wopken, J. Pepijn, Vromans, Martijn J.M., Lens, Susanne M.A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054988/
https://www.ncbi.nlm.nih.gov/pubmed/32027339
http://dx.doi.org/10.1083/jcb.201907087
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author Hadders, Michael A.
Hindriksen, Sanne
Truong, My Anh
Mhaskar, Aditya N.
Wopken, J. Pepijn
Vromans, Martijn J.M.
Lens, Susanne M.A.
author_facet Hadders, Michael A.
Hindriksen, Sanne
Truong, My Anh
Mhaskar, Aditya N.
Wopken, J. Pepijn
Vromans, Martijn J.M.
Lens, Susanne M.A.
author_sort Hadders, Michael A.
collection PubMed
description Aurora B kinase is essential for faithful chromosome segregation during mitosis. During (pro)metaphase, Aurora B is concentrated at the inner centromere by the kinases Haspin and Bub1. However, how Haspin and Bub1 collaborate to control Aurora B activity at centromeres remains unclear. Here, we show that either Haspin or Bub1 activity is sufficient to recruit Aurora B to a distinct chromosomal locus. Moreover, we identified a small, Bub1 kinase–dependent Aurora B pool that supported faithful chromosome segregation in otherwise unchallenged cells. Joined inhibition of Haspin and Bub1 activities fully abolished Aurora B accumulation at centromeres. While this impaired the correction of erroneous KT–MT attachments, it did not compromise the mitotic checkpoint, nor the phosphorylation of the Aurora B kinetochore substrates Hec1, Dsn1, and Knl1. This suggests that Aurora B substrates at the kinetochore are not phosphorylated by centromere-localized pools of Aurora B, and calls for a reevaluation of the current spatial models for how tension affects Aurora B–dependent kinetochore phosphorylation.
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spelling pubmed-70549882020-09-02 Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis Hadders, Michael A. Hindriksen, Sanne Truong, My Anh Mhaskar, Aditya N. Wopken, J. Pepijn Vromans, Martijn J.M. Lens, Susanne M.A. J Cell Biol Article Aurora B kinase is essential for faithful chromosome segregation during mitosis. During (pro)metaphase, Aurora B is concentrated at the inner centromere by the kinases Haspin and Bub1. However, how Haspin and Bub1 collaborate to control Aurora B activity at centromeres remains unclear. Here, we show that either Haspin or Bub1 activity is sufficient to recruit Aurora B to a distinct chromosomal locus. Moreover, we identified a small, Bub1 kinase–dependent Aurora B pool that supported faithful chromosome segregation in otherwise unchallenged cells. Joined inhibition of Haspin and Bub1 activities fully abolished Aurora B accumulation at centromeres. While this impaired the correction of erroneous KT–MT attachments, it did not compromise the mitotic checkpoint, nor the phosphorylation of the Aurora B kinetochore substrates Hec1, Dsn1, and Knl1. This suggests that Aurora B substrates at the kinetochore are not phosphorylated by centromere-localized pools of Aurora B, and calls for a reevaluation of the current spatial models for how tension affects Aurora B–dependent kinetochore phosphorylation. Rockefeller University Press 2020-02-06 /pmc/articles/PMC7054988/ /pubmed/32027339 http://dx.doi.org/10.1083/jcb.201907087 Text en © 2020 Hadders et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Hadders, Michael A.
Hindriksen, Sanne
Truong, My Anh
Mhaskar, Aditya N.
Wopken, J. Pepijn
Vromans, Martijn J.M.
Lens, Susanne M.A.
Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis
title Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis
title_full Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis
title_fullStr Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis
title_full_unstemmed Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis
title_short Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis
title_sort untangling the contribution of haspin and bub1 to aurora b function during mitosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054988/
https://www.ncbi.nlm.nih.gov/pubmed/32027339
http://dx.doi.org/10.1083/jcb.201907087
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