Regulation of Metazoan Chromosome Segregation

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.