Redundant and nonredundant functions of ATM and H2AX in αβ T-lineage lymphocytes.
Redundant and nonredundant functions of ATM and H2AX in αβ T-lineage lymphocytes.
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DOI：
10.4049/jimmunol.1200829
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发表时间：
2012-08-01
期刊：
影响因子：
--
通讯作者：
Bassing CH
中科院分区：
文献类型：
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作者：
Yin B;Lee BS;Yang-Iott KS;Sleckman BP;Bassing CH
The Ataxia Telangiectasia mutated (ATM) kinase and H2AX histone tumor suppressor proteins are each critical for maintenance of cellular genomic stability and suppression of lymphomas harboring clonal translocations. ATM is the predominant kinase that phosphorylates H2AX in chromatin around DNA double strand breaks (DSBs), including along lymphocyte antigen receptor loci cleaved during V(D)J recombination. However, combined germline inactivation of Atm and H2ax in mice causes early embryonic lethality associated with substantial cellular genomic instability, indicating that ATM and H2AX exhibit non-redundant functions in embryonic cells. To evaluate potential non-redundant roles of ATM and H2AX in somatic cells, we generated and analyzed Atm-deficient mice with conditional deletion of H2ax in αβ T-lineage lymphocytes. Combined Atm/H2ax inactivation starting in early-stage CD4−/CD8− thymocytes resulted in lower numbers of later-stage CD4+/CD8+ thymocytes, but led to no discernable V(D)J recombination defect in G1 phase cells beyond that observed in Atm-deficient cells. H2ax deletion in Atm-deficient thymocytes also did not affect the incidence or mortality of mice from thymic lymphomas with clonal chromosome 14 (TCRα/δ) translocations. Yet, in vitro stimulated Atm/H2ax-deficient splenic αβ T-cells exhibited a higher frequency of genomic instability, including radial chromosome translocations and TCRβ translocations, as compared to cells lacking Atm or H2ax. Collectively, our data demonstrate that both redundant and non-redundant functions of ATM and H2AX are required for normal recombination of TCR loci, proliferative expansion of developing thymocytes, and maintenance of genomic stability in cycling αβ T-lineage cells.
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影响因子：
56.9
作者：
Celeste, A;Petersen, S;Nussenzweig, A
通讯作者：
Nussenzweig, A
影响因子：
64.5
作者：
Bassing, CH;Suh, H;Alt, FW
通讯作者：
Alt, FW
DOI：
10.1016/j.bbrc.2007.02.003
发表时间：
2007-04-06
影响因子：
3.1
作者：
Kamimura, Kenya;Ohi, Hiroyuki;Kominami, Ryo
通讯作者：
Kominami, Ryo
影响因子：
21.3
作者：
Fernandez-Capetillo, O;Chen, HT;Nussenzweig, A
通讯作者：
Nussenzweig, A
在发展ATM缺乏的B和T淋巴细胞中，体内编码关节形成的缺陷。
DOI：
10.1084/jem.20061460
发表时间：
2007-06-11
期刊：
The Journal of experimental medicine
影响因子：
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作者：
通讯作者：
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