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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 

 

Read more about research in the Jackson lab.

Watch Steve Jackson describe his research on video.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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