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MPS1 localizes to microtubule-attached kinetochores and actively promotes microtubule release

Daniel Hayward, Emile Roberts, View ORCID ProfileUlrike Gruneberg
doi: https://doi.org/10.1101/2022.05.23.493048
Daniel Hayward
1Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom
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Emile Roberts
1Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom
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Ulrike Gruneberg
1Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom
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  • ORCID record for Ulrike Gruneberg
  • For correspondence: ulrike.gruneberg@path.ox.ac.uk
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Abstract

Summary In eukaryotes, the spindle assembly checkpoint protects genome stability in mitosis by preventing anaphase onset until incorrect microtubule-kinetochore attachment geometries have been eliminated and chromosome biorientation has been completed. These error correction and checkpoint processes are linked by two conserved serine/threonine kinases, Aurora B and MPS1 1, 2. In the prevailing model for spindle checkpoint signaling, MPS1 detects microtubule-free kinetochores generated by the Aurora B-dependent error correction pathway, and initiates spindle checkpoint signaling. However, we find that MPS1 initially localizes to microtubule-attached kinetochores in a manner dependent on the relative activities of Aurora B and its counteracting phosphatase PP2A-B56, and then actively promotes microtubule release. Thus, MPS1 is not a passive sensor for the microtubule binding state of kinetochores but actively generates microtubule-free checkpoint signaling kinetochores. MPS1 is thus instrumental for both the initial resolution of incorrect microtubule-kinetochore attachments and the downstream propagation of spindle checkpoint signaling.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 23, 2022.
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MPS1 localizes to microtubule-attached kinetochores and actively promotes microtubule release
Daniel Hayward, Emile Roberts, Ulrike Gruneberg
bioRxiv 2022.05.23.493048; doi: https://doi.org/10.1101/2022.05.23.493048
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MPS1 localizes to microtubule-attached kinetochores and actively promotes microtubule release
Daniel Hayward, Emile Roberts, Ulrike Gruneberg
bioRxiv 2022.05.23.493048; doi: https://doi.org/10.1101/2022.05.23.493048

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