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However, this detection mechanism also poses a challenge to the host as to how to distinguish foreign DNA from abundant self-DNA. Cyclic guanosine monophosphate (GMP)\u2013adenosine monophosphate (AMP) synthase (cGAS) is a DNA sensor that triggers innate immune responses through production of the second messenger cyclic GMP-AMP (cGAMP), which binds and activates the adaptor protein STING. However, cGAS can be activated by double-stranded DNA irrespective of the sequence, including self-DNA. Although how cGAS is normally kept inactive in cells is still not well understood, recent research has provided strong evidence that genomic DNA damage leads to cGAS activation to stimulate inflammatory responses. This review summarizes recent findings on how genomic instability and DNA damage trigger cGAS activation and how cGAS serves as a link from DNA damage to inflammation, cellular senescence, and cancer.<\/jats:p>","DOI":"10.1084\/jem.20180139","type":"journal-article","created":{"date-parts":[[2018,4,5]],"date-time":"2018-04-05T09:10:09Z","timestamp":1522919409000},"page":"1287-1299","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1259,"title":["The cGAS\u2013cGAMP\u2013STING pathway connects DNA damage to inflammation, senescence, and cancer"],"prefix":"10.1084","volume":"215","author":[{"given":"Tuo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 1"},{"name":"Center for Inflammation Research, University of Texas Southwestern Medical Center, Dallas, TX 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8475-8251","authenticated-orcid":true,"given":"Zhijian J.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 1"},{"name":"Center for Inflammation Research, University of Texas Southwestern Medical Center, Dallas, TX 2"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2018,4,5]]},"reference":[{"key":"2023072609295753900_bib1","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nature12306","article-title":"cGAS produces a 2\u2032-5\u2032-linked cyclic dinucleotide second messenger that activates STING","volume":"498","author":"Ablasser","year":"2013","journal-title":"Nature."},{"key":"2023072609295753900_bib2","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/j.cell.2008.03.038","article-title":"Chemokine signaling via the CXCR2 receptor reinforces senescence","volume":"133","author":"Acosta","year":"2008","journal-title":"Cell."},{"key":"2023072609295753900_bib3","doi-asserted-by":"publisher","first-page":"19386","DOI":"10.1073\/pnas.1215006109","article-title":"STING manifests self DNA-dependent inflammatory disease","volume":"109","author":"Ahn","year":"2012","journal-title":"Proc. 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