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.
Mesh Terms:
Aurora Kinases, Binding Sites, Cell Cycle Proteins, Chromosomal Proteins, Non-Histone, Kinetochores, Mitosis, Nuclear Proteins, Phosphorylation, Protein Binding, Protein Processing, Post-Translational, Schizosaccharomyces, Schizosaccharomyces pombe Proteins
Proc. Natl. Acad. Sci. U.S.A.
Date: Dec. 12, 2016
Download Curated Data For This Publication
217126
Switch View:
  • Interactions 6