CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCC
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,...
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| Format: | Article |
| Language: | English |
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Wiley
2024-09-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406009 |
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| author | Qi Li Qingzhou Chen Tao Zheng Fulin Wang Junlin Teng Haining Zhou Jianguo Chen |
| author_facet | Qi Li Qingzhou Chen Tao Zheng Fulin Wang Junlin Teng Haining Zhou Jianguo Chen |
| author_sort | Qi Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a3d7929ddeff42388b6daf2ea3db6f97 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-a3d7929ddeff42388b6daf2ea3db6f972025-08-20T01:55:16ZengWileyAdvanced Science2198-38442024-09-011135n/an/a10.1002/advs.202406009CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCCQi Li0Qingzhou Chen1Tao Zheng2Fulin Wang3Junlin Teng4Haining Zhou5Jianguo Chen6Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education College of Life Sciences Peking University Beijing 100871 ChinaKey Laboratory of Cell Proliferation and Differentiation of the Ministry of Education College of Life Sciences Peking University Beijing 100871 ChinaKey Laboratory of Cell Proliferation and Differentiation of the Ministry of Education College of Life Sciences Peking University Beijing 100871 ChinaKey Laboratory of Cell Proliferation and Differentiation of the Ministry of Education College of Life Sciences Peking University Beijing 100871 ChinaKey Laboratory of Cell Proliferation and Differentiation of the Ministry of Education College of Life Sciences Peking University Beijing 100871 ChinaKey Laboratory of Epigenetic Regulation and Intervention Institute of Biophysics Chinese Academy of Sciences Beijing 100101 ChinaKey Laboratory of Cell Proliferation and Differentiation of the Ministry of Education College of Life Sciences Peking University Beijing 100871 ChinaAbstract 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.https://doi.org/10.1002/advs.202406009CCDC68CDC20kinetochoremitotic checkpoint complexspindle assembly checkpoint |
| spellingShingle | Qi Li Qingzhou Chen Tao Zheng Fulin Wang Junlin Teng Haining Zhou Jianguo Chen CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCC Advanced Science CCDC68 CDC20 kinetochore mitotic checkpoint complex spindle assembly checkpoint |
| title | CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCC |
| title_full | CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCC |
| title_fullStr | CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCC |
| title_full_unstemmed | CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCC |
| title_short | CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCC |
| title_sort | ccdc68 maintains mitotic checkpoint activation by promoting cdc20 integration into the mcc |
| topic | CCDC68 CDC20 kinetochore mitotic checkpoint complex spindle assembly checkpoint |
| url | https://doi.org/10.1002/advs.202406009 |
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