Phosphorylation of CENP-C by Aurora B facilitates kinetochore attachment error correction in mitosis.
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.
Zhou X, Zheng F, Wang C, Wu M, Zhang X, Wang Q, Yao X, Fu C, Zhang X, Zang J