Affiliation:
1. Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education College of Life Sciences Peking University Beijing 100871 China
2. Key Laboratory of Epigenetic Regulation and Intervention Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China
3. Center for Quantitative Biology Peking University Beijing 100871 China
Abstract
AbstractThe spindle assembly checkpoint (SAC) ensures chromosome segregation fidelity by manipulating unattached kinetochore‐dependent assembly of the mitotic checkpoint complex (MCC). The MCC binds to and inhibits the anaphase promoting complex/cyclosome (APC/C) to postpone mitotic exit. However, the mechanism by which unattached kinetochores mediate MCC formation is not yet fully understood. Here, it is shown that CCDC68 is an outer kinetochore protein that preferentially localizes to unattached kinetochores. Furthermore, CCDC68 interacts with the SAC factor CDC20 to inhibit its autoubiquitination and MCC disassembly. Therefore, CCDC68 restrains APC/C activation to ensure a robust SAC and allow sufficient time for chromosome alignment, thus ensuring chromosomal stability. Hence, the study reveals that CCDC68 is required for CDC20‐dependent MCC stabilization to maintain mitotic checkpoint activation.
Funder
National Natural Science Foundation of China
Key Technologies Research and Development Program