Synthetic lethality between PAXX and XLF in mammalian development.
Synthetic lethality between PAXX and XLF in mammalian development.
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DOI：
10.1101/gad.290510.116
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发表时间：
2016-10-01
影响因子：
10.5
通讯作者：
Jackson SP
中科院分区：
文献类型：
--
作者：
Balmus G;Barros AC;Wijnhoven PW;Lescale C;Hasse HL;Boroviak K;le Sage C;Doe B;Speak AO;Galli A;Jacobsen M;Deriano L;Adams DJ;Blackford AN;Jackson SP
Balmus等人报道，Paxx/Xlf双敲除小鼠表现出与基因组不稳定性、中枢神经系统细胞死亡和淋巴发生几乎完全阻断相关的胚胎致命性，表型与Xrcc4 - / -和Lig4 - / -小鼠非常相似。PAXX是最近在人类细胞中发现的一种新的非同源末端连接DNA修复因子。为了表征其生理作用，我们制造了pax缺陷小鼠。与Xlf - / -小鼠一样，Paxx - / -小鼠可以存活、正常生长和生育，但表现出轻微的放射敏感性。引人注目的是，虽然Paxx缺失与Ku80、Lig4和Atm缺乏症是显性的，但Paxx/Xlf双敲除小鼠表现出与基因组不稳定性、中枢神经系统细胞死亡和淋巴发生几乎完全阻断相关的胚胎致命性，表型与Xrcc4 - / -和Lig4 - / -小鼠非常相似。因此，Paxx和Xlf的联合缺失在哺乳动物中具有合成致死性。
Balmus et al. report that 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. 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.
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DOI：
10.1126/science.1261971
发表时间：
2015-01-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ochi T;Blackford AN;Coates J;Jhujh S;Mehmood S;Tamura N;Travers J;Wu Q;Draviam VM;Robinson CV;Blundell TL;Jackson SP
通讯作者：
Jackson SP
相互作用组分析在非同源末端连接 DNA 修复途径中鉴定出 XRCC4 的新旁系同源物。
影响因子：
16.6
作者：
Xing, Mengtan;Yang, Mingrui;Huo, Wei;Feng, Feng;Wei, Leizhen;Jiang, Wenxia;Ning, Shaokai;Yan, Zhenxin;Li, Wen;Wang, Qingsong;Hou, Mei;Dong, Chunxia;Guo, Rong;Gao, Ge;Ji, Jianguo;Zha, Shan;Lan, Li;Liang, Huanhuan;Xu, Dongyi
通讯作者：
Xu, Dongyi
影响因子：
64.8
作者：
Zha, Shan;Guo, Chunguang;Boboila, Cristian;Oksenych, Valentyn;Cheng, Hwei-Ling;Zhang, Yu;Wesemann, Duane R.;Yuen, Grace;Patel, Harin;Goff, Peter H.;Dubois, Richard L.;Alt, Frederick W.
通讯作者：
Alt, Frederick W.
影响因子：
8.8
作者：
Lescale C;Lenden Hasse H;Blackford AN;Balmus G;Bianchi JJ;Yu W;Bacoccina L;Jarade A;Clouin C;Sivapalan R;Reina-San-Martin B;Jackson SP;Deriano L
通讯作者：
Deriano L
影响因子：
16
作者：
Li, Gang;Alt, Frederick W.;Cheng, Hwei-Ling;Brush, James W.;Goff, Peter H.;Murphy, Mike M.;Franco, Sonia;Zhang, Yu;Zha, Shan
通讯作者：
Zha, Shan