Reference - PMID:29180432 - Phosphorylation of CENP-C by Aurora B facilitates kinetochore attachment error correction in mitosis.

Reference summary

PubMed ID

PMID:29180432

Title

Phosphorylation of CENP-C by Aurora B facilitates kinetochore attachment error correction in mitosis.

Authors

Zhou X, Zheng F, Wang C, Wu M, Zhang X, Wang Q, Yao X, Fu C, Zhang X, Zang J

Citation

Proc Natl Acad Sci U S A 2017 Dec 12;114(50):E10667-E10676

Publication year

2017

Abstract

Kinetochores are superprotein complexes that orchestrate chromosome segregation via a dynamic interaction with spindle microtubules. A physical connection between CENP-C and the Mis12-Ndc80-Knl1 (KMN) protein network is an important pathway that is used to assemble kinetochores on CENP-A nucleosomes. Multiple outer kinetochore components are phosphorylated by Aurora B kinase to activate the spindle assembly checkpoint (SAC) and to ensure accurate chromosome segregation. However, it is unknown whether Aurora B can phosphorylate inner kinetochore components to facilitate proper mitotic chromosome segregation. Here, we reported the structure of the fission yeast Schizosaccharomyces pombe Mis12-Nnf1 complex and showed that N-terminal residues 26-50 in Cnp3 (the CENP-C homolog of S. pombe ) are responsible for interacting with the Mis12 complex. Interestingly, Thr28 of Cnp3 is a substrate of Ark1 (the Aurora B homolog of S. pombe ), and phosphorylation impairs the interaction between the Cnp3 and Mis12 complex. The expression of a phosphorylation-mimicking Cnp3 mutant results in defective chromosome segregation due to improper kinetochore assembly. These results establish a previously uncharacterized regulatory mechanism involved in CENP-C-Mis12-facilitated kinetochore attachment error correction to ensure accurate chromosome segregation during mitosis.

Annotation