{"id":64255,"date":"2023-01-26T18:33:45","date_gmt":"2023-01-26T17:33:45","guid":{"rendered":"https:\/\/cri1149.mlcom-dev.net\/?post_type=publications&#038;p=64255"},"modified":"2025-09-11T16:47:58","modified_gmt":"2025-09-11T14:47:58","slug":"replication-stress-triggered-by-nucleotide-pool-imbalance-drives-dna-damage-and-cgas-sting-pathway-activation-in-nafld","status":"publish","type":"publication","link":"https:\/\/cri1149.mlcom-dev.net\/en\/publication\/replication-stress-triggered-by-nucleotide-pool-imbalance-drives-dna-damage-and-cgas-sting-pathway-activation-in-nafld\/","title":{"rendered":"Replication stress triggered by nucleotide pool imbalance drives DNA damage and cGAS-STING pathway activation in NAFLD"},"content":{"rendered":"","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":false},"class_list":["post-64255","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"[:fr]Dev Cell. [:en]Dev Cell.[:]","date_de_publication":"20220725","numero_doi":"","equipe":[121],"auteurs-liste":[{"texte_libre":true,"auteur-lien":null,"auteur-text":"Romain Donne"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Ma\u00ebva Saroul-Ainama"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Pierre Cordier "},{"texte_libre":false,"auteur-lien":13254,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Christelle Kabore"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Mira Stadler"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Ivan Nemazanyy"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Isabelle Galy-Fauroux"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Mounia Herrag"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Tobias Riedl"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Marie Chansel-Da Cruz"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Stefano Caruso"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"St\u00e9phanie Bonnafous"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Rupert \u00d6llinger"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Roland Rad"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Kristian Unger"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Albert Tran"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Jean-Pierre Couty"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Philippe Gual"},{"texte_libre":false,"auteur-lien":13135,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"S\u00e9verine Celton-Morizur"},{"texte_libre":true,"auteur-lien":null,"auteur-text":" Mathias Heikenwalder "},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Patrick Revy"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Chantal Desdouets"}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/pubmed.ncbi.nlm.nih.gov\/35768000\/"}],"paragraphe":"[:fr]<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\">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.<\/p>\r\n<\/div>[:]","paragraphe_en":"[:fr]<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\">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.<\/p>\r\n<\/div>[:]","documents":null},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Replication stress triggered by nucleotide pool imbalance drives DNA damage and cGAS-STING pathway activation in NAFLD - CRI<\/title>\n<meta name=\"robots\" content=\"noindex, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Replication stress triggered by nucleotide pool imbalance drives DNA damage and cGAS-STING pathway activation in NAFLD - CRI\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cri1149.mlcom-dev.net\/publication\/replication-stress-triggered-by-nucleotide-pool-imbalance-drives-dna-damage-and-cgas-sting-pathway-activation-in-nafld\/\" \/>\n<meta property=\"og:site_name\" content=\"CRI\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/CRI-Centre-de-recherche-sur-linflammation-100116118884153\" \/>\n<meta property=\"article:modified_time\" content=\"2025-09-11T14:47:58+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/replication-stress-triggered-by-nucleotide-pool-imbalance-drives-dna-damage-and-cgas-sting-pathway-activation-in-nafld\/\",\"url\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/replication-stress-triggered-by-nucleotide-pool-imbalance-drives-dna-damage-and-cgas-sting-pathway-activation-in-nafld\/\",\"name\":\"Replication stress triggered by nucleotide pool imbalance drives DNA damage and cGAS-STING pathway activation in NAFLD - 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