RT Journal Article
SR Electronic
T1 cGAS is predominantly a nuclear protein
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 486118
DO 10.1101/486118
A1 Volkman, Hannah E.
A1 Cambier, Stephanie
A1 Gray, Elizabeth E.
A1 Stetson, Daniel B.
YR 2018
UL http://biorxiv.org/content/early/2018/12/04/486118.abstract
AB cGAS is an intracellular innate immune sensor that detects double-stranded DNA. The presence of billions of base pairs of genomic DNA in all nucleated cells raises the question of how cGAS is not constitutively activated. A widely accepted explanation for this is the sequestration of cGAS in the cytosol, which is thought to prevent cGAS from accessing nuclear DNA. Here, we demonstrate that cGAS is predominantly a nuclear protein, regardless of cell cycle phase or cGAS activation status. We show that nuclear cGAS is tethered tightly by a salt-resistant interaction. This tight tethering is independent of the domains required for cGAS activation, and it requires intact nuclear chromatin. We propose that tethering prevents activation of cGAS by genomic DNA, and that it might enable cGAS to distinguish between self DNA and foreign DNA within the nucleus.