Structure and Function of the Centromere and Inner Kinetochore

Accurate chromosome segregation in eukaryotic cells ensures that each daughter cell receives the same chromosome complement during cell division. Key to this process is the kinetochore, a macromolecular complex that connects spindle microtubules to the chromosome. The kinetochore is composed of a diverse array of proteins that can be broadly separated into an inner and outer kinetochore. Each chromosome also contains a distinct site that specifies the location of kinetochore formation, the centromere, which in many species is epigenetically defined by the specialized histone H3 variant centromere protein A (CENP-A). In this Review, we discuss recent advances in determining the complete structure and function of the inner kinetochore, as well as the sequence and 2D and 3D organization of centromeric chromatin. We discuss the implications of these recent advances for our understanding of the assembly and function of the inner kinetochore. We refer readers to a complementary review published in the same issue for a discussion on the structure and function of the outer kinetochore. Finally, we outline key questions persisting in the field driving future studies of the kinetochore and centromere.