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25.10.16 Synthetic-lethal combination of PAXX and XLF loss in mammalian development

last modified Nov 21, 2016 09:17 AM
In this Genes & Development paper, the Jackson group and colleagues demonstrate the combined lethality of PAXX and XLF gene knockouts
25.10.16 Synthetic-lethal combination of PAXX and XLF loss in mammalian development

Excerpt from Fig4A: Cell-death marker accumulates in developing Paxx−/−, Xlf−/− mouse brain.

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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