Principal Investigator Iain Cheeseman
A key goal for the Cheeseman Lab is to define how kinetochores harness the force generated by microtubule depolymerization to direct chromosome alignment and segregation. Our work implicated the KNL1/Mis12 Complex/Ndc80 Complex (KMN) network as an essential player in mediating attachments between kinetochores and microtubules. However, it was unknown how kinetochores remain associated with dynamic microtubule polymers to generate force and direct chromosome movement. We found that the Ndc80 complex lacks the intrinsic ability to remain associated with microtubules as they depolymerize. Importantly, we demonstrated that the human Ska1 complex remains processively associated with depolymerizing microtubules and can impart this tip-tracking activity to the Ndc80 complex. Together, this allows the Ndc80 and Ska1 complexes to form a robust and processive kinetochore-microtubule binding interface. We are currently analyzing the structural and mechanistic basis for these activities. We are also reconstituting larger assemblies of kinetochore components to analyze the ability of the higher order kinetochore structure to harness microtubule-generated force.