Mechanism and Regulation of Kinetochore assembly in budding yeast

• Applicant: Professor Dr. Stefan Westermann
• Subject Area: Cell Biology ; General Genetics and Functional Genome Biology ; Biochemistry
• Term: since 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 310944119

Genome segregation during cell division requires dynamic, regulated interactions between chromosomes and microtubule polymers. For this purpose each chromosome assembles at the centromere a large multisubunit protein complex - the kinetochore. Containing more than 40 structural subunits, kinetochores on the one hand act as sensors that monitor the quality of chromosome-microtubule interactions, support their correction, and coordinate anaphase onset with the cell cycle machinery. On the other hand, kinetochores provide coupling to dynamic microtubule plus-ends in a manner that can drive chromosome motion. How the molecular construction of kinetochores allows mechanochemical signalling and plus-end coupling are key unanswered question. Here we propose to investigate the kinetochore architecture and function in the budding yeast Saccharomyces cerevisiae, using a combination of biochemical reconstitution experiments and genetic analysis. Building on our previous analysis we focus in this proposal on two aspects of kinetochore assembly: First, we will investigate the role of the conserved subunit Mif2/CENP-C during assembly. Second, we will analyze how mitotic kinases control assembly of the COMA complex at kinetochores. Taken together our analysis will provide new mechanistic insights into the fundamental chromosome segregation machinery of the cell.

• DFG Programme: Research Grants