journal article·2024-09Open access

CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCC

Qi Li, Qingzhou Chen, Tao Zheng, Fulin Wang, Junlin Teng, Haining Zhou, Jianguo Chen

Advanced Science· Volume 11· Issue 35

Abstract

Abstract The 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.
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Research context

OpenAlex topics: Microtubule and mitosis dynamics · Genomics and Chromatin Dynamics · Photosynthetic Processes and Mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education College of Life Sciences Peking University Beijing 100871 China

Key Laboratory of Epigenetic Regulation and Intervention Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China

Center for Quantitative Biology Peking University Beijing 100871 China

Funding

National Natural Science Foundation of China · Key Technologies Research and Development Program

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