Synthetic lethality between PAXX and XLF in mammalian development

被引：69

作者：

Balmus, Gabriel ^{[1
,2
]}

Barros, Ana C. ^{[1
,2
]}

Wijnhoven, Paul W. G. ^{[1
,3
]}

Lescale, Chloe ^{[4
,5
]}

Hasse, Helene Lenden ^{[4
,5
]}

Boroviak, Katharina ^{[2
]}

le Sage, Carlos ^{[1
,9
]}

Doe, Brendan ^{[2
]}

Speak, Anneliese O. ^{[2
]}

Galli, Antonella ^{[2
]}

Jacobsen, Matt ^{[6
]}

Deriano, Ludovic ^{[4
,5
]}

Adams, David J. ^{[2
]}

Blackford, Andrew N. ^{[1
,7
,8
]}

Jackson, Stephen P. ^{[1
,2
,3
]}

机构：

[1] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England

[2] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England

[3] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England

[4] Inst Pasteur, Dept Immunol, F-75015 Paris, France

[5] Inst Pasteur, Dept Genomes & Genet, F-75015 Paris, France

[6] AstraZeneca, Cambridge CB4 0FZ, England

[7] Univ Oxford, Weatherall Inst Mol Med, John Radcliffe Hosp, Oxford OX3 9DS, England

[8] Univ Oxford, Dept Oncol, Canc Res UK Med Res Council, Oxford Inst Radiat Oncol, Oxford OX3 7DQ, England

[9] Horizon Discovery, Cambridge Res Pk, Cambridge CB25 9TL, England

来源：

GENES & DEVELOPMENT | 2016年 / 30卷 / 19期

基金：

欧洲研究理事会; 英国惠康基金;

关键词：

ATM; development; NHEJ; PAXX; synthetic lethality; XLF; DNA-LIGASE-IV; V(D)J RECOMBINATION; DAMAGE RESPONSE; DEFICIENT MICE; EMBRYONIC LETHALITY; BREAK REPAIR; KU; XRCC4; IMMUNODEFICIENCY; NEUROGENESIS;

D O I：

10.1101/gad.290510.116

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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 XIf(-/-) 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.

引用

页码：2152 / 2157

页数：6

共 29 条

[1]

XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining [J].