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bioRxiv · 10.1101/627380

CENP-F controls force generation and the dynein-dependent stripping of CENP-E at kinetochores

Auckland, P.·McAinsh, A.
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Abstract

Accurate chromosome segregation demands efficient capture of microtubules by kinetochores and their conversion to stable bi-oriented 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 here that the two microtubule-binding domains make distinct contributions to attachment stability and force generation that are required to minimise errors in anaphase, but are dispensable for congression. We further identify a specialised domain that functions to inhibit the dynein mediated stripping of CENP-E motors. We show how this \"dynein-brake\" is crucial for ensuring kinetochores contain the right number of CENP-E motors at the right time during mitosis, with loss of brake function delaying congression.

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Auckland, P., McAinsh, A.. 2019-05-03. CENP-F controls force generation and the dynein-dependent stripping of CENP-E at kinetochores. https://doi.org/10.1101/627380

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