Novo Nordisk Foundation Center for Protein Research, Unviersity of Copenhagen |
The main focus of the group is to obtain a mechanistic understanding of how key mitotic transitions are regulated to ensure genomic integrity. It is absolutely essential that the duplicated genetic material in the form of chromosomes is segregated equally to the two new daughter cells. Failure in chromosome segregation results in aneuploidy, which is a hallmark of cancer cells and correlates with poor patient prognosis.
Chromosome segregation is achieved by the binding of microtubules of the mitotic spindle to structures on the chromosomes referred to as the kinetochores. It is important that all kinetochores become attached to microtubules before the cell segregates the sister chromatids. The attachment of kinetochores to microtubules is monitored by the Spindle Assembly Checkpoint (SAC) that delays mitotic progression until all kinetochores becomes attached. The SAC acts by inhibiting the large E3 ubiquitin ligase the Anaphase Promoting Complex (APC/C), which prevents the degradation of proteins required for chromosome segregation and mitotic exit. Upon satisfaction of the SAC the APC/C becomes active and in concert with protein phosphatases it coordinates mitotic exit and the generation of the two new daughter cells.