How Does cGAS Avoid Sensing Self-DNA under Normal Physiological Conditions?

cGAS is a cytosolic DNA sensor that activates innate immune responses by producing the second messenger 2′3′-cGAMP, which activates the adaptor STING. cGAS senses dsDNA in a length-dependent but sequence-independent manner, meaning it cannot discriminate self-DNA from foreign DNA. In normal physiolo...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-10, Vol.24 (19), p.14738
Main Authors: Zheng, Wangli, Chen, Nanhua, Meurens, François, Zheng, Wanglong, Zhu, Jianzhong
Format: Article
Language:English
Subjects:
Amino acids
autoimmune diseases
cGAS
Cyclin-dependent kinases
Cytokines
Cytoplasm
DNA
DNA methylation
DNases
Epigenetics
Genetic research
Immune response
Infections
Kinases
mitosis
Phase transitions
Physiological aspects
Physiology
Proteins
Review
self-DNA
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Summary:cGAS is a cytosolic DNA sensor that activates innate immune responses by producing the second messenger 2′3′-cGAMP, which activates the adaptor STING. cGAS senses dsDNA in a length-dependent but sequence-independent manner, meaning it cannot discriminate self-DNA from foreign DNA. In normal physiological conditions, cellular DNA is sequestered in the nucleus by a nuclear envelope and in mitochondria by a mitochondrial membrane. When self-DNA leaks into the cytosol during cellular stress or mitosis, the cGAS can be exposed to self-DNA and activated. Recently, many studies have investigated how cGAS keeps inactive and avoids being aberrantly activated by self-DNA. Thus, this narrative review aims to summarize the mechanisms by which cGAS avoids sensing self-DNA under normal physiological conditions.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241914738