Cancer cells utilize self-inflicted DNA breaks to evade growth limits imposed by exogenous genotoxic stress

Exposure to genotoxic challenge activates cell cycle checkpoints to prevent progression and propagation of deleterious DNA damage. We identify the activity of a nuclease, Caspase-activated DNase (CAD), in promoting G2 checkpoint control in cancer cells via the infliction of DNA breaks. To appreciate the genomic context of these breaks, we performed (genome wide ligation of 3’-hydroxy (OH) ends followed by sequencing), to map the endogenously inflicted DNA breaks following irradiation. GLOE-seq on HCT116 wildtype and CAD-/- cells: Untreated (UT), 20 min post-IR and 24 h post-IR. IR dosage: total of 8Gy given at a dosage rate of 1Gy/min.