KINSIGN · Guarding Genome Stability: Dynamic Control of Chromosome Segregation by Kinetochore Signalling Pathways

Equal segregation of chromosomes during cell division is vital to all life. Using a unique combination of cell biological and biochemical techniques, I will show how an essential set of enzymes promotes error-free chromosome segregation. During each cell division, genetically identical daughter cells are generated by accurate partitioning of the duplicated chromosomes. This relies on proper spatio-temporal execution of various highly dynamic processes. The activity of a small group of enzymes is crucial for at least two of these processes: correct chromosome positioning on the cell's equator prior to cell division and the ability to prevent cell division until every chromosome is thus positioned. The molecular fundamentals of signalling to and from these enzymes will be uncovered by chemical genetics, quantitative (phospho)proteomics, rapid affinity purifications and live-cell deconvolution microscopy. The resulting insights will open research avenues that will ultimately contribute to comprehensive models of how biochemical networks manage to prevent chromosome mis-segregation.