Fig. 3

cGAS is a key linkage between DNA damage and SASP. Exogenous and Endogenous aberrant DNA bind cyclic GMP-AMP synthase (cGAS) and activate the synthesis of 2′3′-cyclic GMP-AMP (2′3′-cGAMP), which binds to and induces oligomerization of STING (stimulator of interferon genes) in the endoplasmic reticulum and its incorporation into vesicles. When STING is activated, it attracts and activates TANK-binding kinase 1 (TBK1), which phosphorylates STING and the interferon regulatory factor IRF3, activating the NF-κB signaling cascade. The sensor kinase ataxia telangiectasia mutated (ATM) also activates TBK1, through the phosphorylation of NF-κB essential modulator (NEMO), a member of the IB kinase complex that activates NF-κB. In response to nuclear DNA damage, ATM can potentially activate STING in a non-canonical manner. PARP-1, poly (ADP-ribose) polymerase 1, is an essential DNA damage sensor. This figure was modified according to the published Fig. 3 in reference [202].