Molecular architecture of the kinetochore–microtubule interface

Top Cited Papers
Publisher Website
Google Scholar
Abstract
The kinetochore is a large proteinaceous structure that mediates interactions between chromosomal DNA and spindle-microtubule polymers. More than 80 kinetochore proteins have been identified using various genetic, functional, cell biology and proteomics approaches. Specialized nucleosomes that contain the histone H3 variant CENP-A form the structural foundation for the kinetochore. A combination of sequence-independent epigenetic mechanisms ensure that CENP-A nucleosomes are directed to centromeres. A combination of proteins form the interface with microtubules and provide distinct functions, including generating a core attachment site, coupling kinetochore movement to disassembling microtubules, affecting the polymerization dynamics of kinetochore-bound microtubules and driving translocation along spindle microtubules. Multiple signalling pathways regulate the fidelity and timing of chromosome segregation and kinetochore function, including the mitotic checkpoint and several mitotic kinases.