Polß modulates the expression of type I interferon via STING pathway.
Biochem Biophys Res Commun
; 621: 137-143, 2022 09 17.
Article
in En
| MEDLINE
| ID: mdl-35834922
ABSTRACT
DNA Polymerase ß (Polß) is a key enzyme in base excision repair (BER), which is very important in maintaining the stability and integrity of the genome. Mutant Polß is closely associated with carcinogenesis. However, Polß is highly expressed in most cancers, but the underlying mechanism is not well understood. Here, we found that breast cancer cells MCF-7 with Polß knockdown exhibited high levels of type I interferon and were easily eliminated by natural killer (NK) cells.Similarly, Polß-mutant (R137Q) mice exhibited chronic inflammation symptoms in multiple organs and upregulated type I interferon levels. Further results showed that Polß deficiency caused more DNA damage accumulation in cells and triggered the leakage of damaged DNA into the cytoplasm, which activated the STING/IRF3 pathway, promoted phosphorylated IRF3 translocating into the nucleus and enhanced the expression of type I interferon and proinflammatory cytokines. In addition, this effect could be eliminated by Polß overexpression, STING inhibitor or STING knockdown. Taken together, our findings provide mechanistic insight into the role of Polß in cancers by linking DNA repair and the inflammatory STING pathway.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interferon Type I
/
DNA Polymerase beta
Limits:
Animals
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2022
Type:
Article
Affiliation country:
China