Timing the decision to override a checkpoint

Cellular decision-making is a complex, dynamic process critical for survival and adaptation. Despite its significance, the timing of these decisions remains poorly understood, both functionally and mechanistically. One particularly high-stakes decision arises in the context of DNA damage, where cells must choose between halting proliferation to repair damage or overriding checkpoints to continue division. This choice determines not only the immediate fate of the cell —survival or death— but also its competitive standing within the population. In this talk, I will share insights from our investigation into how Saccharomyces cerevisiae (budding yeast) times the decision to override the DNA damage checkpoint. We explore the cellular mechanisms that integrate temporal information with quantitative signals of DNA damage, enabling cells to make context-dependent, optimal decisions. Our findings reveal how cells weigh the trade-offs between repair and proliferation, offering an understanding of the interplay between timing, signaling, and cellular outcomes.