CENP-C-Mis12 complex establishes a regulatory loop through Aurora B for chromosome segregation
Establishing the correct kinetochore-microtubule attachment is crucial for faithful chromosome segregation. The kinetochore has various regulatory mechanisms for establishing correct bipolar attachment. However, how the regulations are coupled is not fully understood. Here, we demonstrate a regulatory loop between the kinetochore protein CENP-C and Aurora B kinase, which is critical for the error correction of kinetochore-microtubule attachment. This regulatory loop is mediated through the binding of CENP-C to the outer kinetochore Mis12 complex (Mis12C). Although the Mis12C-binding region of CENP-C is dispensable for mouse development and proliferation in human RPE-1 cells, those cells lacking this region display increased mitotic defects. The CENP-C-Mis12C interaction facilitates the centromeric recruitment of Aurora B and the mitotic error correction in human cells. Given that Aurora B reinforces the CENP-C-Mis12C interaction, our findings reveal a positive regulatory loop between Aurora B recruitment and the CENP-C-Mis12C interaction, which ensures chromosome biorientation for accurate chromosome segregation.
Authors
- Yuichi Wakabayashi (ORCID: https://orcid.org/0000-0002-8861-2954)
- Toshihiko Fujimori (ORCID: https://orcid.org/0000-0001-5200-4634)
- Yasuhiro Hirano (ORCID: https://orcid.org/0000-0001-7339-4053)
- Yurika Tokunaga (ORCID: https://orcid.org/0000-0001-6625-6824)
- Jiahang Miao (ORCID: https://orcid.org/0000-0002-4926-2090)
- Masakazu Hashimoto (ORCID: https://orcid.org/0000-0002-9617-4843)
- Kazuhiro Okumura (ORCID: https://orcid.org/0000-0002-4980-3125)
- Tatsuo Fukagawa (ORCID: https://orcid.org/0000-0001-8564-6852)
- Yusuke Takenoshita (ORCID: https://orcid.org/0000-0002-0720-815X)
- Hiroshi Sasaki (ORCID: https://orcid.org/0000-0001-8752-6846)
- Masatoshi Hara (ORCID: https://orcid.org/0000-0001-8433-1111)
- Weixia Kong
Institutions
- Fukushima Medical University (JP)
- National Institute for Basic Biology (JP)
- Chiba Institute of Science (JP)
- The Graduate University for Advanced Studies, SOKENDAI (JP)
- Ube Frontier University (JP)
- Chiba Cancer Center (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- Life Science Alliance
- Published
- 2024-10-21
- DOI
- https://doi.org/10.26508/lsa.202402927
- Citations
- 6
- Primary Topic
- Microtubule and mitosis dynamics
- Type
- article
- Field-Weighted Citation Impact
- 1.96
Funders
- Takeda Science Foundation
- Daiichi Sankyo Foundation of Life Science
- Japan Society for the Promotion of Science
- Core Research for Evolutional Science and Technology
- National Institute for Basic Biology
- Daiichi Sankyo Europe