Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice.
Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice.
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DOI：
10.1083/jcb.201204098
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发表时间：
2012-08-06
期刊：
影响因子：
--
通讯作者：
Zha S
中科院分区：
文献类型：
--
作者：
Yamamoto K;Wang Y;Jiang W;Liu X;Dubois RL;Lin CS;Ludwig T;Bakkenist CJ;Zha S
Expression of a kinase-deficient ATM protein leads to severe genomic instability and embryonic lethality. Ataxia telangiectasia (A-T) mutated (ATM) kinase orchestrates deoxyribonucleic acid (DNA) damage responses by phosphorylating numerous substrates implicated in DNA repair and cell cycle checkpoint activation. A-T patients and mouse models that express no ATM protein undergo normal embryonic development but exhibit pleiotropic DNA repair defects. In this paper, we report that mice carrying homozygous kinase-dead mutations in Atm (AtmKD/KD) died during early embryonic development. AtmKD/− cells exhibited proliferation defects and genomic instability, especially chromatid breaks, at levels higher than Atm−/− cells. Despite this increased genomic instability, AtmKD/− lymphocytes progressed through variable, diversity, and joining recombination and immunoglobulin class switch recombination, two events requiring nonhomologous end joining, at levels comparable to Atm−/− lymphocytes. Together, these results reveal an essential function of ATM during embryogenesis and an important function of catalytically inactive ATM protein in DNA repair.
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影响因子：
16
作者：
Callen, Elsa;Jankovic, Mila;Wong, Nancy;Zha, Shan;Chen, Hua-Tang;Difilippantonio, Simone;Di Virgilio, Michela;Heidkamp, Gordon;Alt, Frederick W.;Nussenzweig, Andre;Nussenzweig, Michel
通讯作者：
Nussenzweig, Michel
DOI：
10.1083/jcb.201204035
发表时间：
2012-08-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Daniel JA;Pellegrini M;Lee BS;Guo Z;Filsuf D;Belkina NV;You Z;Paull TT;Sleckman BP;Feigenbaum L;Nussenzweig A
通讯作者：
Nussenzweig A
影响因子：
4.3
作者：
Callen, Elsa;Bunting, Sam;Nussenzweig, Andre
通讯作者：
Nussenzweig, Andre
影响因子：
3.5
作者：
Gilad, S;Khosravi, R;BarShira, A
通讯作者：
BarShira, A
影响因子：
3.9
作者：
Barone, Giancarlo;Groom, Alix;Taylor, A. Malcolm R.
通讯作者：
Taylor, A. Malcolm R.