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Subthreshold perturbation of DNA replication induces a secretory response and a bystander effect in naïve human fibroblasts

Replication stress is a hallmark of cancer, where it drives DNA damage and genome instability. Yet subtle, subthreshold perturbations of DNA synthesis likely occur routinely in normal proliferating tissues, and their consequences for cell homeostasis are unknown. Using primary human fibroblasts, we show that doses of the DNA polymerase inhibitor aphidicolin, too low to engage the replication…

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