PuSH - Publikationsserver des Helmholtz Zentrums München: Replication stress triggered by nucleotide pool imbalance drives DNA damage and cGAS-STING pathway activation in NAFLD.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Donne, R.* ; Saroul-Ainama, M.* ; Cordier, P.* ; Hammoutene, A.* ; Kabore, C.* ; Stadler, M.* ; Nemazanyy, I.* ; Galy-Fauroux, I.* ; Herrag, M.* ; Riedl, T.* ; Chansel-Da Cruz, M.* ; Caruso, S.* ; Bonnafous, S.* ; Öllinger, R.* ; Rad, R.* ; Unger, K. ; Tran, A.* ; Couty, J.P.* ; Gual, P.* ; Paradis, V.* ; Celton-Morizur, S.* ; Heikenwalder, M.* ; Revy, P.* ; Desdouets, C.*

Replication stress triggered by nucleotide pool imbalance drives DNA damage and cGAS-STING pathway activation in NAFLD.

Dev. Cell 57, 1728-1741.e6 (2022)

Verlagsversion

Postprint

DOI

PMC

	Open Access Green

Abstract
Metriken
Zusatzinfos

Non-alcoholic steatotic liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD has a major effect on the intrinsic proliferative properties of hepatocytes. Here, we investigated the mechanisms underlying the activation of DNA damage response during NAFLD. Proliferating mouse NAFLD hepatocytes harbor replication stress (RS) with an alteration of the replication fork's speed and activation of ATR pathway, which is sufficient to cause DNA breaks. Nucleotide pool imbalance occurring during NAFLD is the key driver of RS. Remarkably, DNA lesions drive cGAS/STING pathway activation, a major component of cells' intrinsic immune response. The translational significance of this study was reiterated by showing that lipid overload in proliferating HepaRG was sufficient to induce RS and nucleotide pool imbalance. Moreover, livers from NAFLD patients displayed nucleotide pathway deregulation and cGAS/STING gene alteration. Altogether, our findings shed light on the mechanisms by which damaged NAFLD hepatocytes might promote disease progression.

Impact Factor

Scopus SNIP

Scopus
Cited By

Altmetric

13.417

0.000