Synthetic lethality between PAXX and XLF in mammalian development
Balmus, G et al. (2016) Genes & Dev. 2016. 30: 2152-2157 DOI:10.1101/gad.290510.116
Exploring the role of recently discovered PAXX, a factor in the cellular pathway that repairs DNA double-strand breaks, the Jackson group and colleagues show that loss of PAXX in combination with loss of XLF in mice is a lethal combination despite the mild health effects that result from loss of either factor alone.
Abstract from paper
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.
Abstract reproduced under Creative Commons License CC-BY-4.0
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