The kinetochore and the centromere: a working long distance relationship

Accurate chromosome segregation is a prerequisite for the maintenance of the genomic stability. Consequently, elaborate molecular machineries and mechanisms emerged during the course of evolution in order to ensure proper division of the genetic material. The kinetochore, an essential multiprotein complex assembled on mitotic or meiotic centromeres, is an example of such machinery. Recently considerable progress has been made in understanding their composition, the recruitment hierarchy of their components, and the principles of their regulation. However, these advances are accompanied by a growing number of unanswered questions about the function of the individual subunits and of how the structure of the different subcomplexes relates to function. Here we review our rapidly growing knowledge on interacting networks of structural and regulatory proteins of the metazoan mitotic kinetochore: its centromeric foundations, its structural core, its components that interact with spindle microtubules and the spindle assembly checkpoint.