» Articles » PMID: 29976794

DNA-induced Liquid Phase Condensation of CGAS Activates Innate Immune Signaling

Overview
Journal Science
Specialty Science
Date 2018 Jul 7
PMID 29976794
Citations 413
Authors
Affiliations
Soon will be listed here.
Abstract

The binding of DNA to cyclic GMP-AMP synthase (cGAS) leads to the production of the secondary messenger cyclic GMP-AMP (cGAMP), which activates innate immune responses. We have shown that DNA binding to cGAS robustly induced the formation of liquidlike droplets in which cGAS was activated. The disordered and positively charged cGAS N terminus enhanced cGAS-DNA phase separation by increasing the valencies of DNA binding. Long DNA was more efficient in promoting cGAS liquid phase separation and cGAS enzyme activity than short DNA. Moreover, free zinc ions enhanced cGAS enzyme activity both in vitro and in cells by promoting cGAS-DNA phase separation. These results demonstrated that the DNA-induced phase transition of cGAS promotes cGAMP production and innate immune signaling.

Citing Articles

Induction of translation-suppressive G3BP1 stress granules and interferon-signaling cGAS condensates by transfected plasmid DNA.

Majerciak V, Zheng Z Hlife. 2025; 3(1):21-37.

PMID: 40078969 PMC: 11902918. DOI: 10.1016/j.hlife.2024.11.005.


Multi-omics analysis identifies a liquid-liquid phase separation-related subtypes in head and neck squamous cell carcinoma.

Zhai P, Chen M, Wang Q, Zhao J, Tang X, Lu C Front Oncol. 2025; 15:1509810.

PMID: 40078192 PMC: 11897011. DOI: 10.3389/fonc.2025.1509810.


Zinc-copper bimetallic nanoplatforms trigger photothermal-amplified cuproptosis and cGAS-STING activation for enhancing triple-negative breast cancer immunotherapy.

Zhou B, Chen M, Hao Z, Li L, Zhang Y, Fang B J Nanobiotechnology. 2025; 23(1):137.

PMID: 39994712 PMC: 11849371. DOI: 10.1186/s12951-025-03186-4.


[Latest Findings on the Role of Liquid-Liquid Phase Separation in the Regulation of Immune Cell Activation and Key Signaling].

Li J, Zhou C Sichuan Da Xue Xue Bao Yi Xue Ban. 2025; 55(6):1527-1532.

PMID: 39990825 PMC: 11839372. DOI: 10.12182/20241160302.


A novel biosensor for the spatiotemporal analysis of STING activation during innate immune responses to dsDNA.

Smarduch S, Moreno-Velasquez S, Ilic D, Dadsena S, Morant R, Ciprinidis A EMBO J. 2025; .

PMID: 39984755 DOI: 10.1038/s44318-025-00370-y.


References
1.
Li P, Banjade S, Cheng H, Kim S, Chen B, Guo L . Phase transitions in the assembly of multivalent signalling proteins. Nature. 2012; 483(7389):336-40. PMC: 3343696. DOI: 10.1038/nature10879. View

2.
Civril F, Deimling T, de Oliveira Mann C, Ablasser A, Moldt M, Witte G . Structural mechanism of cytosolic DNA sensing by cGAS. Nature. 2013; 498(7454):332-7. PMC: 3768140. DOI: 10.1038/nature12305. View

3.
Milo R . What is the total number of protein molecules per cell volume? A call to rethink some published values. Bioessays. 2013; 35(12):1050-5. PMC: 3910158. DOI: 10.1002/bies.201300066. View

4.
Eide D . Zinc transporters and the cellular trafficking of zinc. Biochim Biophys Acta. 2006; 1763(7):711-22. DOI: 10.1016/j.bbamcr.2006.03.005. View

5.
Kuhn T, Ihalainen T, Hyvaluoma J, Dross N, Willman S, Langowski J . Protein diffusion in mammalian cell cytoplasm. PLoS One. 2011; 6(8):e22962. PMC: 3158749. DOI: 10.1371/journal.pone.0022962. View