LONGCHROM

The main goal of this proposal is to achieve a detailed understanding of the mechanisms coordinating chromosome segregation and cytokinesis. Key to this task will be the experimental manipulation of chromosome architecture in budding yeast, which allows the generation of cells with extra long chromosome arms. Using this strategy, we have already uncovered at least one novel feedback system, which coordinates axial chromosome compaction with anaphase spindle size. We will characterize this and other anaphase controls through a multidisciplinary approach, which combines classical molecular and genetic techniques with state-of-the-art genomics and proteomics, and an extensive set of reagents we have developed to analyze cell division dynamics and chromosome segregation in living cells. We will identify the mechanisms coordinating chromosome arm length with spindle size, and the molecular basis of chromosome segregation errors during anaphase. The relevance of these novel processes will be confirmed by analysis of cell division in animal cells and in a Drosophila tumour model. These approaches will significantly advance our understanding of how eukaryotic cells coordinate cytokinesis with chromosome segregation, how they prevent aneuploidy and genetic instability, and will ultimately be instrumental to identify new therapeutic targets for human cancer.