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CENP-F stabilizes kinetochore-microtubule attachments and limits dynein stripping of corona cargoes

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Auckland, Philip, Roscioli, Emanuele, Coker, H. L. E. and McAinsh, Andrew D. (2020) CENP-F stabilizes kinetochore-microtubule attachments and limits dynein stripping of corona cargoes. Journal of Cell Biology, 219 (5). e201905018. doi:10.1083/jcb.201905018 ISSN 0021-9525.

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Official URL: https://doi.org/10.1083/jcb.201905018

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Abstract

Accurate chromosome segregation demands efficient capture of microtubules by kinetochores and their conversion to stable bioriented attachments that can congress and then segregate chromosomes. An early event is the shedding of the outermost fibrous corona layer of the kinetochore following microtubule attachment. Centromere protein F (CENP-F) is part of the corona, contains two microtubule-binding domains, and physically associates with dynein motor regulators. Here, we have combined CRISPR gene editing and engineered separation-of-function mutants to define how CENP-F contributes to kinetochore function. We show that the two microtubule-binding domains make distinct contributions to attachment stability and force transduction but are dispensable for chromosome congression. We further identify a specialized domain that functions to limit the dynein-mediated stripping of corona cargoes through a direct interaction with Nde1. This antagonistic activity is crucial for maintaining the required corona composition and ensuring efficient kinetochore biorientation.

Item Type: Journal Article
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Chromosomes, Microtubules, Centromere, CRISPR (Genetics)
Journal or Publication Title: Journal of Cell Biology
Publisher: Rockefeller University Press
ISSN: 0021-9525
Official Date: 24 March 2020
Dates:
DateEvent
24 March 2020Published
19 February 2020Accepted
Volume: 219
Number: 5
Article Number: e201905018
DOI: 10.1083/jcb.201905018
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 30 March 2020
Date of first compliant Open Access: 31 March 2020
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
106151/Z/14/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269
208384/Z/17/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269
WM150020Royal Societyhttp://dx.doi.org/10.13039/501100000288
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