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Cell cycle control and genome integrity
The de Bruin lab's mission is to establish fundamental principles of cell cycle control involved in the maintenance of genome stability and cancer initiation and development. The lab has used a wide range of model organisms and approaches with a final goal of finding ways to identify and exploit therapeutic opportunities for cancer’s addiction to growth and proliferation. Our group has established the molecular mechanism by which G1/S transcription is inactivated during S phase and how it is maintained in response to replication stress. Our work indicates that G1/S transcription plays an essential role in the tolerance to replication stress. Since replication stress is a major cause of genomic instability in cancer, this represents a crucial new area for cancer studies in the lab. We recently established that cellular growth has a central role in determining CDK inhibitor sensitivity. This work suggests that independent of increased CDK activity, when cell division is inhibited, but cell growth continues, cells simply get too big to maintain a proliferative state or maintain genome stability. Since enhanced growth signalling is common in cancers, this helps explain the anti-cancer efficacy of CDK inhibitors. This new insight is now being used to ask more specific questions to understand the mechanisms that determine a cell’s sensitivity to CDK inhibitors.