Centromere/kinetochore is assembled through CENP-C oligomerization.

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• The kinetochore is vital for accurate chromosome segregation during cell division.
• The constitutive centromere-associated network (CCAN) is a kinetochore subcomplex that binds centromeric chromatin.
• CENP-C is a key CCAN protein proposed as a central hub for centromere/kinetochore organization.

Purpose of the Study:

• To elucidate the role of CENP-C in the assembly of the CCAN.
• To investigate the structural and functional significance of CENP-C domains, particularly the Cupin domain.

Main Methods:

• Demonstration of chicken CENP-C function using its CCAN-binding and C-terminal Cupin domains.
• Structural and biochemical analyses to study protein self-oligomerization.
• Assessment of CENP-C's impact on CCAN localization and centromeric chromatin organization.

Main Results:

• Both the CCAN-binding domain and the C-terminal Cupin domain of CENP-C are necessary and sufficient for its function.
• Structural and biochemical data revealed self-oligomerization of the CENP-C Cupin domain in both chicken and human.
• Oligomerization of the CENP-C Cupin domain is essential for CENP-C function, CCAN centromeric localization, and centromeric chromatin organization.

Conclusions:

• CENP-C facilitates centromere/kinetochore assembly through its self-oligomerization capability.
• The Cupin domain-mediated oligomerization is a critical mechanism for CENP-C's role in organizing centromeric chromatin and ensuring proper chromosome segregation.