DNA damage is a potent inducer of inflammation. While this is well accepted, with the example of UV-induced DNA damage, a detailed understanding of the machineries at play in this inflammatory effect remains elusive. We have recently discovered that DNA damage promoted by enzymatic recombination and DNA intercalation resulted in induction of type-I interferon (IFN) responses in various cell types through activation of the cytosolic cyclic GMP-AMP synthase (cGAS) pathway (Pepin et al., Nucleic Acids Research 2016, and Pepin et al., Nucleic Acids Research 2017). In the present work, we identify a novel role for viral oncogenes in the facilitation of cGAS sensing and IFN production following DNA damage promoted by genotoxic agents and UV exposure. We also demonstrate that UV-driven DNA damage can propagate inflammation horizontally to adjacent cells through gap junction transfer of cyclic GMP-AMP (cGAMP). Our on-going studies collectively suggest a critical role for the cGAS pathway in the transcriptional regulation of IFN responses to DNA damage, potentially at play in UV-driven skin inflammation seen in systemic lupus erythematosus. Because drugs approved for use in humans can inhibit this horizontal amplification of inflammation, our work has the potential to help address select diseases where DNA damage is at the root of aberrant inflammation.