Figure 1.

cGAS-STING pathway activation by replicative stress. Two different pathways can trigger cGAS-STING activation by replicative stress: (1) the formation of micronuclei and (2) the accumulation of replication fork-derived DNA in the cytoplasm. These events will trigger the activation of cGAS, which produces cGAMP, activating the STimulator of INterferon Genes (STING) protein. Once activated, STING recruits TBK1 that is then able to phosphorylate its different targets that include Interferon Regulatory Factor 3 (IRF3) and different members of the NF-κB signalling pathway. This culminates in an upregulation of pro-inflammatory factors.