Fig. 6
From: Dysregulation of the low-level replication stress response in transformed cell lines
Different responses of cancer and primary cells to replication stress. Upper panel: Below a particular threshold of stress intensity, primary cells induce the LoL-DDR, which is a noncanonical stress response that produces RIR, triggering detoxification in an adaptive way. Above this threshold, the cells induce the cDDR and detoxify RIR10. Both responses protect genome stability. Lower panel: In cancer cells, these responses are dysregulated, and ROS levels continuously increase with increasing stress intensity, resulting in the accumulation of premutagenic oxidative lesions (8-oxoG). Since ROS induce replication stress15,17, this reciprocally triggers vicious circle of replication stress and ROS production, which promote genome instability, potentially fueling tumor initiation and progression.
