Review
Version 1
Preserved in Portico This version is not peer-reviewed
How Does cGAS Avoid to Sense Self-DNA under Normal Physiological Conditions?
Version 1
: Received: 22 August 2023 / Approved: 23 August 2023 / Online: 24 August 2023 (07:12:24 CEST)
A peer-reviewed article of this Preprint also exists.
Zheng, W.; Chen, N.; Meurens, F.; Zheng, W.; Zhu, J. How Does cGAS Avoid Sensing Self-DNA under Normal Physiological Conditions? Int. J. Mol. Sci. 2023, 24, 14738. Zheng, W.; Chen, N.; Meurens, F.; Zheng, W.; Zhu, J. How Does cGAS Avoid Sensing Self-DNA under Normal Physiological Conditions? Int. J. Mol. Sci. 2023, 24, 14738.
Abstract
cGAS is a cytosolic DNA sensor that activates innate immune responses through production of the second messenger 2’3’-cGAMP, which activates the adaptor STING. cGAS senses dsDNA in a length-dependent but sequence-independent manner, and it cannot discriminate self-DNA from foreign DNA. In normal physiological conditions, cellular DNA is sequestered in the nucleus by nuclear envelope and in mitochondria by mitochondrial membrane. When self-DNA leaks into the cytosol during cellular stress, or during mitosis, the cGAS can be exposed to self-DNA and be activated. Recently, many studies have investigated how cGAS keeps inactive and avoids to be aberrantly activated by self-DNA. Thus, the aim of this narrative review is to summarize the mechanisms by which cGAS avoids to sense self-DNA under normal physiological conditions.
Keywords
cGAS; self-DNA; mitosis; autoimmune diseases; DNases
Subject
Biology and Life Sciences, Animal Science, Veterinary Science and Zoology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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