Related Experiment Video
Updated: Jan 2, 2026

DNA-Tethered RNA Polymerase for Programmable In vitro Transcription and Molecular Computation
Published on: December 29, 2021
Tight nuclear tethering of cGAS is essential for preventing autoreactivity
Hannah E Volkman1, Stephanie Cambier1, Elizabeth E Gray1
1Department of Immunology, University of Washington School of Medicine, Seattle, United States.
Abstract:
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 endogenous 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 identify the evolutionarily conserved tethering surface on cGAS and we show that mutation of single amino acids within this surface renders cGAS massively and constitutively active against self-DNA. Thus, tight nuclear tethering maintains the resting state of cGAS and prevents autoreactivity.
Related Concept Videos
Cooperative Binding of Transcription Regulators
Cooperative Binding of Transcription Regulators
GTPases and their Regulation
Large G-proteins,...
GTPases and their Regulation
Activation and Inactivation of G Proteins
Attachment of Sister Chromatids

