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cGAS is activated by DNA in a length‐dependent manner
Author(s) -
Luecke Stefanie,
Holleufer Andreas,
Christensen Maria H,
Jønsson Kasper L,
Boni Gerardo A,
Sørensen Lambert K,
Johannsen Mogens,
Jakobsen Martin R,
Hartmann Rune,
Paludan Søren R
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744017
Subject(s) - dna , microbiology and biotechnology , chemistry , biology , genetics
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 ds DNA 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.