An Analysis of Spindle Microtubule Interactions Mediated by the Ndc80 Complex, Cep57R and Cep57

During mitosis, kinetochores link centromeric DNA to spindle microtubules to facilitate accurate segregation of the replicated genome. Spindle poles also must form stable microtubule attachments to generate the opposing forces required for the depolymerization-coupled movement of chromosomes during anaphase. Kinetochores contain between 80-100 proteins, but the mechanism by which this macromolecular structure couples to microtubules remains unknown. Models invoking a kinetochore sleeve, a sliding ring and a fibrillar coupler have been proposed to explain how the kinetochore harnesses the energy released by a depolymerizing microtubule to power chromosome movements. In this dissertation we test two of these models through extensive study of two proteins thought to function as key kinetochore couplers.

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