cGAS is activated by DNA in a length-dependent manner

被引：244

作者：

Luecke, Stefanie ^{[1
]}

Holleufer, Andreas ^{[2
]}

Christensen, Maria H. ^{[1
]}

Jonsson, Kasper L. ^{[1
]}

Boni, Gerardo A. ^{[1
]}

Sorensen, Lambert K. ^{[3
]}

Johannsen, Mogens ^{[3
]}

Jakobsen, Martin R. ^{[1
]}

Hartmann, Rune ^{[2
]}

Paludan, Soren R. ^{[1
]}

机构：

[1] Aarhus Univ, Dept Biomed, Aarhus, Denmark

[2] Aarhus Univ, Dept Mol Biol & Genet, Aarhus, Denmark

[3] Aarhus Univ Hosp, Dept Forens Med, Aarhus, Denmark

来源：

EMBO REPORTS | 2017年 / 18卷 / 10期

关键词：

cGAS; DNA sensing; interferon; length dependence; STING; CYCLIC GMP-AMP; ANTIVIRAL DEFENSE; SENSOR CGAS; RIG-I; RECOGNITION; SYNTHASE; IFI16; 2ND-MESSENGER; FILAMENTS; PATHWAY;

D O I：

10.15252/embr.201744017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cytosolic DNA stimulates innate immune responses, including type I interferons (IFN), which have antiviral and immunomodulatory activities. Cyclic GMP-AMP synthase (cGAS) recognizes cytoplasmic DNA and signals via STING to induce IFN production. Despite the importance of DNA in innate immunity, the nature of the DNA that stimulates IFN production is not well described. Using low DNA concentrations, we show that dsDNA induces IFN in a length-dependent manner. This is observed over a wide length-span of DNA, ranging from the minimal stimulatory length to several kilobases, and is fully dependent on cGAS irrespective of DNA length. Importantly, in vitro studies reveal that long DNA activates recombinant human cGAS more efficiently than short DNA, showing that length-dependent DNA recognition is an intrinsic property of cGAS independent of accessory proteins. Collectively, this work identifies long DNA as the molecular entity stimulating the cGAS pathway upon cytosolic DNA challenge such as viral infections.

引用

页码：1707 / 1715

页数：9

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