Speaker
Description
Gene expression models often treat the cell cycle as mere background, overlooking the transient gene-dosage shifts introduced by DNA replication. We ask how these dosage changes reshape the time it takes single cells to cross regulatory thresholds—a key currency for decision-making in transcriptional networks. Using a general stochastic framework that captures cell-to-cell variability without relying on system-specific details, we examine how replication-induced changes in effective synthesis rates modulate timing distributions. We find that replication timing can systematically advance or delay threshold crossings and, depending on network context, either sharpen or broaden variability across cells. These effects are most consequential for circuits that gate events requiring precise schedules, such as division checkpoints or developmental transitions. Our analysis highlights qualitative design principles for buffering or leveraging replication-driven noise and suggests inference strategies to disentangle replication from other sources of stochasticity. By placing DNA replication back into the picture, we reveal a general mechanism by which the cell cycle sculpts single-cell temporal coordination.
