Radiation is one of the most successful cancer solutions. On the other hand, gastrointestinal (GI) syndrome MAO can be a major limiting aspect in abdominal and pelvic radiotherapy. The loss of crypt stem cells or villus endothelial cells continues to be suggested to get responsible for radiation-induced intestinal injury. We report right here a significant function from the BH3-only protein p53 upregulated ABT-199 buy modulator of apoptosis (PUMA) inside the radiosensitivity of intestinal epithelium and pathogenesis of GI syndrome. PUMA was induced in a p53-dependent method and mediated radiation-induced apoptosis by means of the mitochondrial pathway from the intestinal mucosa. PUMA-deficient mice exhibited blocked apoptosis while in the intestinal progenitor and stem cells, enhanced crypt proliferation and regeneration, and prolonged survival following lethal doses of radiation. Unexpectedly, PUMA deficiency had little effect on radiation-induced intestinal endothelial apoptosis. Suppressing PUMA expression by antisense oligonucleotides offered significant intestinal radioprotection. Consequently, PUMA-mediated apoptosis while in the progenitor and stem cell compartments is critical for radiation-induced intestinal damage.