FBS Colloquia No.279Laboratory of Chromosome Biology

The complicated protein-protein interaction network of the kinetochore, which ensures accurate chromosome segregation

During mitotic cell division, chromosomes, which are careers of genetic materials, must be divided into daughter cells. Failure of the process can lead to chromosome instabilities that cause many diseases, including cancer. The kinetochore is a macromolecular complex that connects the centromeric DNA to spindle microtubules for accurate chromosome segregation during cell division. Although the kinetochore functions appear to be simple, the protein-protein interaction network in the kinetochore is complicated. The microtubule-binding complex called the KMN (Knl1, Mis12, and Ndc80 complexes) network is recruited onto the kinetochore during mitosis by CENP-C or CENP-T, which constitutively localizes to the centromere: the CENP-C and CENP-T pathways. We previously found that the CENP-T pathway is a major pathway for recruiting the KMN network onto the kinetochore in chicken DT40 cells. However, since the CENP-C pathway partially compensates for the functions of the CENP-T pathway, it has been hard to elucidate how the KMN network functions on the CENP-T. Here, we clarified the functional roles of the KMN network on CENP-T by dissecting the protein-protein interaction network on the CENP-T pathway, using various genome engineering techniques. In this talk, I would like to demonstrate and discuss the roles of the CENP-T pathway, which ensures accurate chromosome segregation.