Fig. 3
From: Ligands stimulating antitumour immunity as the next G-quadruplex challenge
G4 binders increase R-loop-dependent genome instability activating then the cGAS/STING/IRF3 pathway in cancer cells. Mechanism of G4-binders activity in cancer cells. A) G4 binders target G4 structures by stabilizing the G-loop. B) G-loops can induce double strand breaks through either replication- and transcription-dependent mechanisms, resulting in cell senescence or micronuclei induction. C) Micronuclei are recognized by DNA sensing protein cGAS, leading to activation of cGAS/STING pathway and to IRF3- regulated gene expression. D) The phosphorylated form of IRF3 translocates to the nucleus and promotes IFNB expression in cancer cells. IFNB secretion allows its binding to a membrane interferon receptor and consequent IFNB-dependent transcriptional cascade activation.