FBS Colloquia No.419Laboratory of Chromosome Biology

Toward a Structural Understanding of Kinetochore Clustering

The kinetochore is a large protein complex assembled at the centromere of each chromosome that ensures accurate chromosome segregation during eukaryotic cell division. It consists of two major components: the constitutive centromere-associated network (CCAN) and the KMN network. Each kinetochore contains multiple copies of CCAN; however, despite recent advances in cryo-EM single-particle analysis that have revealed the structures of individual CCAN subcomplexes, how these units assemble into a higher-order functional kinetochore in cells remains a fundamental open question.

To address this question, we have investigated the role of CENP-C in CCAN clustering. CENP-C serves as a central scaffold within the CCAN and provides multiple protein–protein interaction interfaces. In this seminar, I will present our recent findings on the molecular basis underlying CCAN higher-order assembly, obtained through an interdisciplinary approach combining molecular dynamics simulations, biochemistry, and cell biology.