PAXX was identified recently as a novel nonhomologous end-joining DNA repair factor in human cells. To characterize its physiological roles, we generated Paxx-deficient mice. Like Xlf-/- mice, Paxx-/- mice are viable, grow normally, and are fertile but show mild radiosensitivity. Strikingly, while Paxx loss is epistatic with Ku80, Lig4, and Atm deficiency, Paxx/Xlf double-knockout mice display embryonic lethality associated with genomic instability, cell death in the central nervous system, and an almost complete block in lymphogenesis, phenotypes that closely resemble those of Xrcc4-/- and Lig4-/- mice. Thus, combined loss of Paxx and Xlf is synthetic-lethal in mammals.
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ATM, NHEJ, PAXX, XLF, development, synthetic lethality, Animals, Apoptosis, DNA-Binding Proteins, Embryonic Development, Epistasis, Genetic, Genomic Instability, Mice, Mice, Inbred C57BL, Mice, Knockout, Protein Kinases, Radiation Tolerance, Synthetic Lethal Mutations, Trisaccharides