Principal Investigator Terry Orr-Weaver
We exploited the superb chromosome cytology in Drosophila mitotic and meiotic cells to identify mutants affecting chromosome segregation and to define the normal functions of their protein products. From a collection of mutants that arrest mitosis in embryogenesis we found several affecting kinetochore proteins. The Drosophila MEI-S332 protein is the founding member of the Shugoshin protein family, whose members bind to the centromere and maintain sister-chromatid cohesion by protecting cohesin. We are studying the regulation of centromere localization of MEI-S332 that is dynamically controlled by phosphorylation. Phosphorylation of MEI-S332 by the Aurora B kinase subunit of the Chromosome Passenger Complex is needed for stable localization of MEI-S332 to the centromere. Dissociation of MEI-S332 from the centromere at anaphase of mitosis and anaphase II of meiosis requires its phosphorylation by POLO kinase.