Science https://doi.org/10.1126/science.aat1022 (2018)

The cyclic GMP-AMP synthase cGAS is an intracellular sensor that detects cytosolic double-stranded DNA. Binding to DNA activates the enzymatic activity of cGAS and leads to accumulation of the cyclic dinucleotide GAMP, which in turn activates a signaling cascade dependent on the adaptor STING that results in the production of type I interferons. In Science, Du and Chen report that cGAS undergoes a liquid-like phase transition after binding to DNA but not after binding to duplex RNA. This liquid-droplet formation is dependent on zinc ions. Long DNA duplexes are more efficient than short DNA duplexes in promoting the formation of cGAS puncta in vivo. The phase transition of cGAS to liquid droplets results in greater enzymatic specific activity and thus more efficient activation of type I interferon responses.