FBS Colloquia No.220Laboratory of Chromosome Biology

Dynamic CCAN-centromere interaction during the cell cycle progression: its regulation and function

Chromosomes, which are the vehicles of genetic heredity, have to be duplicated in S-phase and equally segregated into daughter cells during M-phase in the cell cycle progression. One of crucial factors, which ensure the accurate chromosome segregation, is the kinetochore that is a large protein complex assembled on the centromere of each chromosome. The kinetochore binds to spindle microtubules and connects with chromosomes. Defects in the kinetochore results in chromosome missegregation, leading to aneuploidy that causes genetic disorders including cancer. Therefore, understanding of structure and function of the kinetochore is important not only for preventing from the genetic disorders but also for answering a fundamental biological question “how are chromosomes accurately segregated?” The kinetochore in vertebrates consists of more than a hundred of proteins, which make protein interaction networks to bridge between centromere and microtubules. It has been well studied how the kinetochore interacts with the microtubules. In contrast, however, molecular details on kinetochore-centromere interaction has been less studied. CCAN (constitutive centromere-associated network), a kinetochore subcomplex, provides a kinetochore-centromere interaction interface and localizes to centromere throughout the cell cycle. CENP-C, a CCAN component, directly binds to centromeric chromatin. Because CCAN constitutively localizes to centromeres, CENP-C appeared to stably bind to centromeric chromatin during cell cycle. However, we previously found that CENP-C changes interaction to centromeric chromatin during the cell cycle progression. Here, I will present our recent results on molecular mechanisms of how CENP-C-centromeric chromatin interaction is regulated. I would also like to discuss differences of necessity of CCAN-centromere interaction for chromosome segeregation among species.