Cyclic GMP-AMP (cGAMP) synthase (cGAS) was identified as a cytosolic DNA sensor, which induced STING-mediated induction of type I interferon (Sun L et al. 2013). Knockdown of cGAS inhibited IRF3 activation and IFN-beta production in human acute monocytic leukemia cell line (THP1) in response to DNA transfection or DNA virus infection. Affinity-purified human or mouse cGAS proteins from transfected human embryonic kidney HEK293T cells were able to catalyze the production of cGAMP in vitro, which stimulated IRF3 dimerization in mouse Raw264.7 cells (mouse Abelson murine leukemia virus-induced tumor cell line). The catalytic activity of cGAS was shown to depend on the presence of DNA (Sun L et al. 2013). Sun L et al. suggested that sGAS acts as a cytosolic DNA sensor, which triggers type I interferon induction by producing the second messenger cGAMP in mammalian cells.