A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition

To achieve chromosome segregation during mitosis, sister chromatids must undergo a dramatic change in their behavior to switch from balanced oscillations at the metaphase plate to directed poleward motion during anaphase. However, the factors that alter chromosome behavior at the metaphase-to-anapha...

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Main Authors: Su, Kuan-Chung, Schweizer, Nina, Maiato, Helder, Bathe, Mark, Barry, Zachary Thomas, Cheeseman, Iain M
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: Elsevier 2017
Online Access:http://hdl.handle.net/1721.1/107423
https://orcid.org/0000-0002-6199-6855
https://orcid.org/0000-0001-8844-7170
https://orcid.org/0000-0002-3829-5612
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author Su, Kuan-Chung
Schweizer, Nina
Maiato, Helder
Bathe, Mark
Barry, Zachary Thomas
Cheeseman, Iain M
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Su, Kuan-Chung
Schweizer, Nina
Maiato, Helder
Bathe, Mark
Barry, Zachary Thomas
Cheeseman, Iain M
author_sort Su, Kuan-Chung
collection MIT
description To achieve chromosome segregation during mitosis, sister chromatids must undergo a dramatic change in their behavior to switch from balanced oscillations at the metaphase plate to directed poleward motion during anaphase. However, the factors that alter chromosome behavior at the metaphase-to-anaphase transition remain incompletely understood. Here, we perform time-lapse imaging to analyze anaphase chromosomedynamics in human cells. Using multiple directed biochemical, genetic, and physical perturbations, our results demonstrate that differences in the global phosphorylation states between metaphase and anaphase are the major determinant of chromosome motion dynamics. Indeed, causing a mitotic phosphorylation state to persist into anaphase produces dramatic metaphase-like oscillations. These induced oscillations depend on both kinetochore-derived and polar ejection forces that oppose poleward motion. Thus, our analysis of anaphase chromosome motion reveals that dephosphorylation of multiple mitotic substrates is required to suppress metaphase chromosome oscillatory motions and achieve directed poleward motion for successful chromosome segregation.
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spelling mit-1721.1/1074232022-10-01T20:08:38Z A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition Su, Kuan-Chung Schweizer, Nina Maiato, Helder Bathe, Mark Barry, Zachary Thomas Cheeseman, Iain M Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Bathe, Mark Barry, Zachary Thomas Cheeseman, Iain M To achieve chromosome segregation during mitosis, sister chromatids must undergo a dramatic change in their behavior to switch from balanced oscillations at the metaphase plate to directed poleward motion during anaphase. However, the factors that alter chromosome behavior at the metaphase-to-anaphase transition remain incompletely understood. Here, we perform time-lapse imaging to analyze anaphase chromosomedynamics in human cells. Using multiple directed biochemical, genetic, and physical perturbations, our results demonstrate that differences in the global phosphorylation states between metaphase and anaphase are the major determinant of chromosome motion dynamics. Indeed, causing a mitotic phosphorylation state to persist into anaphase produces dramatic metaphase-like oscillations. These induced oscillations depend on both kinetochore-derived and polar ejection forces that oppose poleward motion. Thus, our analysis of anaphase chromosome motion reveals that dephosphorylation of multiple mitotic substrates is required to suppress metaphase chromosome oscillatory motions and achieve directed poleward motion for successful chromosome segregation. National Institute of General Medical Sciences (U.S.) (GM088313) National Science Foundation (U.S.) (PoLS PHY 1305537) Leukemia & Lymphoma Society of America Marie Curie/Erwin Schrodinger Fellowship of the Austrian Science Fund (J-3478) American Cancer Society (121776) European Research Council FLAD Life Science 2020 Fondation Louis-Jeantet 2017-03-15T19:22:37Z 2017-03-15T19:22:37Z 2016-11 2016-09 Article http://purl.org/eprint/type/JournalArticle 22111247 http://hdl.handle.net/1721.1/107423 Su, Kuan-Chung, Zachary Barry, Nina Schweizer, Helder Maiato, Mark Bathe, and Iain McPherson Cheeseman. “A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition.” Cell Reports 17, no. 7 (November 2016): 1728–1738. https://orcid.org/0000-0002-6199-6855 https://orcid.org/0000-0001-8844-7170 https://orcid.org/0000-0002-3829-5612 en_US http://dx.doi.org/10.1016/j.celrep.2016.10.046 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier
spellingShingle Su, Kuan-Chung
Schweizer, Nina
Maiato, Helder
Bathe, Mark
Barry, Zachary Thomas
Cheeseman, Iain M
A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition
title A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition
title_full A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition
title_fullStr A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition
title_full_unstemmed A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition
title_short A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition
title_sort regulatory switch alters chromosome motions at the metaphase to anaphase transition
url http://hdl.handle.net/1721.1/107423
https://orcid.org/0000-0002-6199-6855
https://orcid.org/0000-0001-8844-7170
https://orcid.org/0000-0002-3829-5612
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