Cellular resilience to DNA replication stress
Genome duplication for cell division is an enormous undertaking and a major source of cancer-associated genome instability. Moreover, the replication machinery is a common target in certain cancer therapies that aim at generating elevated levels of replication stress in rapidly dividing cells. We are interested in the cellular mechanisms that define the replication capacity of cells and determine their natural resilience to replication stress. When key factors become limiting, cells cannot maintain a stable replication program, resulting in a catastrophic shattering of the genome. Using automated multi-parameter cell imaging, we strive to identify novel modulators of replication stress resilience and characterize their molecular functions.
Toledo LI, Altmeyer M, Rask MB et al.
ATR prohibits replication catastrophe by preventing global exhaustion of RPA