Highly conserved multiprotein assemblies known as kinetochores orchestrate chromosome segregation during cell division and ensure that DNA is correctly transmitted from one generation to the next. Kinetochores act directly by assembling onto chromatin regions named centromeres. Activities governed by kinetochores include establishing centromeric heterochromatin, holding sister chromatids together via centromeric cohesin, nucleating kinetochore microtubules, attaching and orienting sister chromatids to spindle microtubules, sensing the tension or occupancy resulting from chromatid-microtubule attachment, recruiting spindle checkpoint components to induce a mitotic delay when tension/occupancy is absent, separating sister chromatids along the spindle, and regulating the initiation of cytokinesis. Kinetochore defects generate cells with abnormal numbers of chromosomes resulting in genetic disease, cancer formation/progression or even death of the cell or organism. Likely because they manage so many roles, kinetochores are some of the most complex intracellular structures known today. Understanding how kinetochores coordinate chromosome segregation requires the identification of their components and the characterization of how they assemble into a competent mechanochemical structure. This chapter discusses our current understanding of how kinetochore components recognize and assemble onto centromeric regions. We will discuss similarities and differences between both processes in various species. However, as the budding yeast and vertebrate kinetochores have been studied most intensely, their kinetochores will be discussed in greatest detail.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)