Chaves-Pérez, AlmudenaYilmaz, MahmutPerna, Cristiande la Rosa, SergioDjouder, Nabil2024-02-082024-02-082019-05-31Science . 2019 ;364(6443):eaaq1165.http://hdl.handle.net/20.500.12105/17555Ionizing radiation (IR) can cause gastrointestinal syndrome (GIS), a lethal disorder, by means of unknown mechanisms. We show that high-dose irradiation increases unconventional prefoldin RPB5 interactor (URI) levels in mouse intestinal crypt, but organ regeneration correlates with URI reductions. URI overexpression in intestine protects mice from radiation-induced GIS, whereas halving URI expression sensitizes mice to IR. URI specifically inhibits β-catenin in stem cell-like label-retaining (LR) cells, which are essential for organ regeneration after IR. URI reduction activates β-catenin-induced c-MYC expression, causing proliferation of and DNA damage to LR cells, rendering them radiosensitive. Therefore, URI labels LR cells which promote tissue regeneration in response to high-dose irradiation, and c-MYC inhibitors could be countermeasures for humans at risk of developing GIS.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Radiation ToleranceRegenerationAnimalsGastrointestinal DiseasesGene Knock-In TechniquesIntestinal MucosaMiceMice, Inbred C57BLMice, Mutant StrainsRadiation InjuriesRadiation, IonizingReceptors, G-Protein-CoupledRepressor Proteinsbeta CateninAttribution-NonCommercial-NoDerivatives 4.0 Internacional31147493364644310.1126/science.aaq11651095-9203Science (New York, N.Y.)open access