Cep57 is a Mis12-interacting kinetochore protein involved in kinetochore targeting of Mad1-Mad2.

Abstract:

:The spindle assembly checkpoint (SAC) arrests cells in mitosis by sensing unattached kinetochores, until all chromosomes are bi-oriented by spindle microtubules. Kinetochore accumulation of the SAC component Mad1-Mad2 is crucial for SAC activation. However, the mechanism by which Mad1-Mad2 accumulation at kinetochores is regulated is not clear. Here we find that Cep57 is localized to kinetochores in human cells, and binds to Mis12, a KMN (KNL1/Mis12 complex/Ndc80 complex) network component. Cep57 also interacts with Mad1, and depletion of Cep57 results in decreased kinetochore localization of Mad1-Mad2, reduced SAC signalling and increased chromosome segregation errors. We also show that the microtubule-binding activity of Cep57 is involved in the timely removal of Mad1 from kinetochores. Thus, these findings reveal that the KMN network-binding protein Cep57 is a mitotic kinetochore component, and demonstrate the functional connection between the KMN network and the SAC.

journal_name

Nat Commun

journal_title

Nature communications

authors

Zhou H,Wang T,Zheng T,Teng J,Chen J

doi

10.1038/ncomms10151

subject

Has Abstract

pub_date

2016-01-08 00:00:00

pages

10151

issn

2041-1723

pii

ncomms10151

journal_volume

7

pub_type

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