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Kinetochores accelerate or delay APC/C activation by directing Cdc20 to opposing fates.

ABSTRACT: Mitotic duration is determined by activation of the anaphase-promoting complex/cyclosome (APC/C) bound to its coactivator, Cdc20. Kinetochores, the microtubule-interacting machines on chromosomes, restrain mitotic exit when not attached to spindle microtubules by generating a Cdc20-containing complex that inhibits the APC/C. Here, we show that flux of Cdc20 through kinetochores also accelerates mitotic exit by promoting its dephosphorylation by kinetochore-localized protein phosphatase 1, which allows Cdc20 to activate the APC/C. Both APC/C activation and inhibition depend on Cdc20 fluxing through the same binding site at kinetochores. The microtubule attachment status of kinetochores therefore optimizes mitotic duration by controlling the balance between opposing Cdc20 fates.

SUBMITTER: Kim T

PROVIDER: S-EPMC5538432 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Kinetochores accelerate or delay APC/C activation by directing Cdc20 to opposing fates.

Kim Taekyung T Lara-Gonzalez Pablo P Prevo Bram B Meitinger Franz F Cheerambathur Dhanya K DK Oegema Karen K Desai Arshad A

Genes & development 20170601 11

Mitotic duration is determined by activation of the anaphase-promoting complex/cyclosome (APC/C) bound to its coactivator, Cdc20. Kinetochores, the microtubule-interacting machines on chromosomes, restrain mitotic exit when not attached to spindle microtubules by generating a Cdc20-containing complex that inhibits the APC/C. Here, we show that flux of Cdc20 through kinetochores also accelerates mitotic exit by promoting its dephosphorylation by kinetochore-localized protein phosphatase 1, which ...[more]

PMID: 28698300

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