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oai:repisalud.isciii.es:20.500.12105/175552024-11-29T13:39:53Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Chaves-Pérez, Almudena author Yilmaz, Mahmut author Perna, Cristian author de la Rosa, Sergio author Djouder, Nabil author 2019-05-31 Ionizing 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. Science . 2019 ;364(6443):eaaq1165. 10.1126/science.aaq1165 1095-9203 Science (New York, N.Y.) 31147493 http://hdl.handle.net/20.500.12105/17555 URI is required to maintain intestinal architecture during ionizing radiation.