BAF restricts cGAS on nuclear DNA to prevent innate immune activation.
Science
; 369(6505): 823-828, 2020 08 14.
Article
in En
| MEDLINE
| ID: mdl-32792394
ABSTRACT
The appearance of DNA in the cytosol is perceived as a danger signal that stimulates potent immune responses through cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS). How cells regulate the activity of cGAS toward self-DNA and guard against potentially damaging autoinflammatory responses is a fundamental biological question. Here, we identify barrier-to-autointegration factor 1 (BAF) as a natural opponent of cGAS activity on genomic self-DNA. We show that BAF dynamically outcompetes cGAS for DNA binding, hence prohibiting the formation of DNA-cGAS complexes that are essential for enzymatic activity. Upon acute loss of nuclear membrane integrity, BAF is necessary to restrict cGAS activity on exposed DNA. Our observations reveal a safeguard mechanism, distinct from physical separation, by which cells protect themselves against aberrant immune responses toward genomic DNA.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA
/
Cell Nucleus
/
DNA-Binding Proteins
/
Immunity, Innate
/
Nucleotidyltransferases
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Science
Year:
2020
Document type:
Article
Affiliation country:
Switzerland