Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway

Lijun Sun, Jiaxi Wu, Fenghe Du, Xiang Chen, Zhijian J. Chen

Research output: Contribution to journalArticle

1446 Scopus citations

Abstract

The presence of DNA in the cytoplasm of mammalian cells is a danger signal that triggers host immune responses such as the production of type I interferons. Cytosolic DNA induces interferons through the production of cyclic guanosine monophosphate-adenosine monophosphate (cyclic GMP-AMP, or cGAMP), which binds to and activates the adaptor protein STING. Through biochemical fractionation and quantitative mass spectrometry, we identified a cGAMP synthase (cGAS), which belongs to the nucleotidyltransferase family. Overexpression of cGAS activated the transcription factor IRF3 and induced interferon-β in a STING-dependent manner. Knockdown of cGAS inhibited IRF3 activation and interferon-β induction by DNA transfection or DNA virus infection. cGAS bound to DNA in the cytoplasm and catalyzed cGAMP synthesis. These results indicate that cGAS is a cytosolic DNA sensor that induces interferons by producing the second messenger cGAMP.

Original languageEnglish (US)
Pages (from-to)786-791
Number of pages6
JournalScience
Volume339
Issue number6121
DOIs
StatePublished - Feb 15 2013

ASJC Scopus subject areas

  • General

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