Centromere/kinetochore is assembled through CENP-C oligomerization

Kinetochore is an essential protein complex required for accurate chromosome segregation. The constitutive centromere-associated network (CCAN), a subcomplex of the kinetochore, associates with centromeric chromatin and provides a platform for the kinetochore assembly. The CCAN protein CENP-C is tho...

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Bibliographic Details
Published in:Molecular cell 2023-07, Vol.83 (13), p.2188-2205.e13
Main Authors: Hara, Masatoshi, Ariyoshi, Mariko, Sano, Tomoki, Nozawa, Ryu-Suke, Shinkai, Soya, Onami, Shuichi, Jansen, Isabelle, Hirota, Toru, Fukagawa, Tatsuo
Format: Article
Language:English
Subjects:
CCAN
CENP-C
centromere
chromosome segregation
kinetochore assembly
oligomerization
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Summary:Kinetochore is an essential protein complex required for accurate chromosome segregation. The constitutive centromere-associated network (CCAN), a subcomplex of the kinetochore, associates with centromeric chromatin and provides a platform for the kinetochore assembly. The CCAN protein CENP-C is thought to be a central hub for the centromere/kinetochore organization. However, the role of CENP-C in CCAN assembly needs to be elucidated. Here, we demonstrate that both the CCAN-binding domain and the C-terminal region that includes the Cupin domain of CENP-C are necessary and sufficient for chicken CENP-C function. Structural and biochemical analyses reveal self-oligomerization of the Cupin domains of chicken and human CENP-C. We find that the CENP-C Cupin domain oligomerization is vital for CENP-C function, centromeric localization of CCAN, and centromeric chromatin organization. These results suggest that CENP-C facilitates the centromere/kinetochore assembly through its oligomerization. [Display omitted] •CENP-C domains that are required and sufficient for its function are defined•CENP-C is oligomerized through the Cupin domain and its extended region•CENP-C oligomerization is required for cell viability and mitotic progression•CENP-C oligomerization is crucial for centromere/kinetochore assembly Hara et al. find that CENP-C, a centromeric protein, is oligomerized through the Cupin domain in its C-terminal region. The oligomerization of the Cupin domain is essential for CENP-C function to localize CCAN proteins to centromeres and assemble kinetochore and centromeric chromatin.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2023.05.023