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. 2021 Aug 9;13(2):90–101. doi: 10.1007/s13238-021-00869-0

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Canonical role of cytosolic cGAS and non-canonical role of nuclear cGAS. In the cytosol, cGAS is activated by self- or non-self dsDNAs, leading to dimerization-induced activation and cGAMP production, which in turn promotes IFN gene expression by activating the STING-TBK1-IRF3 axis. The binding of cGAMP to STING also leads to the activation of the IKK/NFκB pathway, resulting in inflammatory gene expression. In the nucleus, cGAS is localized at DSB, the replication fork, centromere, and/or nucleosome where it carries out the nonconical roles beyond innate immune function