Inner Kinetochore Protein Facilitates Kinetochore-Microtubule Attachment Error Correction during Mitosis

Sister chromatids are equally distributed into two daughter cells during mitosis to ensure faithful transmission of genetic materials. Defects in segregation of sister chromatids lead to aneuploid or polyploid cells, which are intermediates in the progression of many human solid tumors and hallmarks of reproductive diseases and aging. Faithful chromosome segregation during mitosis requires the accurate interaction of kinetochore with microtubule in a bi-polar manner. Spindle assembly checkpoint/Error correction pathways monitor the connection between kinetochore and microtubule to ensure proper kinetochore-microtubule attachment. Previous work showed that Aurora B kinase is one of the essential components of these pathways, which phosphorylates the outer kinetochore proteins to promote the establishment of appropriate kinetochore-microtubule attachments. However, none of the inner kinetochore proteins has been shown as the substrate of Aurora B and involved in Spindle assembly checkpoint/Error correction pathways. Recently, a collaborative study led by Dr. ZANG Jianye and Dr. FU Chuanhai of the University of Science and Technology of China has revealed the molecular mechanism underlying the CENP-C-dependent kinetochore recruitment of Mis12 complex, which is negatively regulated by Aurora B-dependent phosphorylation of inner kinetochore protein CENP-C and involved in Spindle assembly checkpoint/Error correction pathways (Figure 1). Their work establishes a previously uncharacterized regulatory mechanism involved in CENP-C–Mis12-facilitated kinetochore attachment error correction to ensure accurate chromosome segregation during mitosis. Some of the qualification of phosphorylation was carried on the mass spectrometric end-station of the National Synchrotron Radiation Laboratory. This work was published in Proc. Natl. Acad. Sci. U. S. A.(PNAS [114]:E10667-E10676).

Aurora B-dependent phosphorylation of inner kinetochore protein CENP-C Facilitates Kinetochore-Microtubule Attachment Error Correction