DNA is normally localized to the nucleus, so its cytoplasmic localization sends off alarm bells to the immune system because it indicates that a virus may have entered. But how does the immune system actually detect the DNA (see the Perspective by O’Neill)? Sun et al. identify cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) synthase (cGAS), which can bind to cytoplasmic DNA directly and catalyze the production of cGAMP. cGAMP then acts as a second messenger to activate downstream signaling events that trigger antiviral immunity. Wu et al. show that cGAMP, produced in response to cytoplasmic DNA, binds to and activates the signaling adaptor protein STING.
J. Wu, L. Sun, X. Chen, F. Du, H. Shi, C. Chen, Z. J. Chen, Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 339, 826–830 (2013). [Abstract] [Full Text]