Architecture of microtubule-chromosome interface: how far we are to build it
ABSTRACT :
Precise partitioning of duplicated chromosomes into daughter cells is crucial to prevent aneuploidy, a hallmark of many tumors and hereditary birth defects. In order to achieve correct and faithful segregation, the chromosomes need to maintain a stable yet flexible connection between their kinetochores and the spindle microtubules during mitosis. This is achieved by tightly regulated and presumably through hierarchical interactions between a wide array of proteins of both the kinetochore and the microtubules at the microtubule-kinetochore interface. However, given that the microtubules are extremely dynamic structures that stochastically switch between polymerization and depolymerization and moreover, the kinetochore also exhibits dynamic organization and exchange within its components, a specialized molecular machine is likely to be necessary to couple the chromosome movement to the dynamic microtubules and maintain the required tension. In this talk, I will summarize the recent developments in identifying the components of this molecular machine and their mechanisms action during chromosome segregation. Based on our findings and of other investigators worldwide, I will further discuss on the possible architecture of this molecular driver.