The molecular basis of tight nuclear tethering and inactivation of cGAS.

ABSTRACT: Nucleic acids derived from pathogens induce potent innate immune responses^1-6. Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA sensor that catalyses the synthesis of the cyclic dinucleotide cyclic GMP-AMP, which mediates the induction of type I interferons through the STING-TBK1-IRF3 signalling axis^7-11. cGAS was previously thought to not react with self DNA owing to its cytosolic localization^2,12,13; however, recent studies have shown that cGAS is localized mostly in the nucleus and has low activity as a result of tight nuclear tethering^14-18. Here we show that cGAS binds to nucleosomes with nanomolar affinity and that nucleosome binding potently inhibits its catalytic activity. To elucidate the molecular basis of cGAS inactivation by nu

SUBMITTER: Zhao B 

PROVIDER: S-EPMC7704945 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature