{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Schumann T"],"funding":["Aicardi-Goutières Syndrome Advocacy Association","Deutsche Forschungsgemeinschaft","Fritz-Thyssen-Stiftung"],"pagination":["e20220829"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9648672"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["220(1)"],"pubmed_abstract":["Defects in nucleic acid metabolizing enzymes can lead to spontaneous but selective activation of either cGAS/STING or RIG-like receptor (RLR) signaling, causing type I interferon-driven inflammatory diseases. In these pathophysiological conditions, activation of the DNA sensor cGAS and IFN production are linked to spontaneous DNA damage. Physiological, or tonic, IFN signaling on the other hand is essential to functionally prime nucleic acid sensing pathways. Here, we show that low-level chronic DNA damage in mice lacking the Aicardi-Goutières syndrome gene SAMHD1 reduced tumor-free survival when crossed to a p53-deficient, but not to a DNA mismatch repair-deficient background. Increased DNA damage did not result in higher levels of type I interferon. Instead, we found that the chronic inte"],"journal":["The Journal of experimental medicine"],"pubmed_title":["Deficiency for SAMHD1 activates MDA5 in a cGAS/STING-dependent manner."],"pmcid":["PMC9648672"],"funding_grant_id":["Az. 10.19.1.013 MN","BE-5877/2-1","401821119/GRK 2504","369799452-TRR237"],"pubmed_authors":["Schumann T","Shakeri F","Lienenklaus S","Gerbaulet A","Muller P","Hajikazemi M","Schubert N","Badstubner M","Mayo MA","Manel N","Schmitz M","Kato H","Gramberg T","Ge Y","Bauer S","Ramon SC","Ada SR","Rupp L","Behrendt R","Utess B","Maser KI","Sydow L","Roers A","Rupf B","Paeschke K","Buness A","Muhandes L","Hartmann G","Haase M","Zillinger T","Hega M"],"additional_accession":[]},"is_claimable":false,"name":"Deficiency for SAMHD1 activates MDA5 in a cGAS/STING-dependent manner.","description":"Defects in nucleic acid metabolizing enzymes can lead to spontaneous but selective activation of either cGAS/STING or RIG-like receptor (RLR) signaling, causing type I interferon-driven inflammatory diseases. In these pathophysiological conditions, activation of the DNA sensor cGAS and IFN production are linked to spontaneous DNA damage. Physiological, or tonic, IFN signaling on the other hand is essential to functionally prime nucleic acid sensing pathways. Here, we show that low-level chronic DNA damage in mice lacking the Aicardi-Goutières syndrome gene SAMHD1 reduced tumor-free survival when crossed to a p53-deficient, but not to a DNA mismatch repair-deficient background. Increased DNA damage did not result in higher levels of type I interferon. Instead, we found that the chronic inte","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-05-27T10:52:06.096Z","creation":"2025-04-04T11:27:01.106Z"},"accession":"S-EPMC9648672","cross_references":{"pubmed":["36346347"],"doi":["10.1084/jem.20220829"]}}