cGAS-cCAMP-STING axis, Sensor of cytosolic dsDNA

http://jem.rupress.org/content/215/5/1287

Citate.” It is now well established that cGAS is a major sensor of microbial pathogens that contain DNA or generate DNA in their life cycles. New studies have illuminated an equally critical role of cGAS in the surveillance of self-DNA that mislocalizes to the cytoplasm under pathological conditions. Although decades of research have led to a good understanding of how genotoxic stress and genomic instability regulate DNA damage repair, cell cycle checkpoints, and programmed cell death, the mechanism by which DNA damage leads to inflammation and autoimmunity was not well understood until recently. In retrospect, it is logical that cGAS is well positioned to connect nuclear DNA damage to immune responses because cGAS can be activated by any dsDNA that enters the cytoplasm. It is interesting to note that in addition to chemical and radiation damage to DNA, many other biological processes such as oncogene activation, telomere shortening, and cell division errors all impinge on DNA. Although NF-κB is well known to play an important role in mediating inflammatory responses to DNA damage (Janssens and Tschopp, 2006), the link between DNA and NF-κB was not clear. Now cGAS has emerged as an important link between DNA damage and activation of NF-κB, IRF3, and likely other transcription factors.”