Synthetic lethality between PAXX and XLF in mammalian development.

Abstract:: 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.

Authors:: G Balmus, AC Barros, PWG Wijnhoven, C Lescale, HL Hasse, K Boroviak, C le Sage, B Doe, AO Speak, A Galli, M Jacobsen, L Deriano, DJ Adams, AN Blackford, SP Jackson

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