Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination In vivo.
Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination In vivo.
复制标题
DOI：
10.1084/jem.186.6.921
复制
发表时间：
1997-09-15
期刊：
影响因子：
--
通讯作者：
Li GC
中科院分区：
文献类型：
--
作者：
Ouyang H;Nussenzweig A;Kurimasa A;Soares VC;Li X;Cordon-Cardo C;Li Wh;Cheong N;Nussenzweig M;Iliakis G;Chen DJ;Li GC
Ku是两种蛋白质Ku 70和Ku 80的复合物，作为异二聚体结合DNA双链断裂（DSB）并激活DNA依赖性蛋白激酶。Ku 70亚基在DNA DSB修复、电离辐射超敏反应和V（D）J重组中的作用在缺乏Ku 70（Ku 70 −/−）的小鼠中进行了检查。与Ku 80 −/−小鼠一样，Ku 70 −/−小鼠在DNA DSB修复方面表现出严重的缺陷，并且是比例侏儒。令人惊讶的是，与T淋巴细胞和B淋巴细胞发育在早期阶段被抑制的Ku 80 −/−小鼠相反，Ku 70的缺乏与T细胞受体基因重组以及成熟的CD 4 + CD 8 −和CD 4 − CD 8 + T细胞的发育是一致的。我们的数据首次表明，Ku 70在DNA DSB修复中起重要作用，但不是TCR V（D）J重组所必需的。这些结果表明，不同但重叠的修复途径可能介导DNA DSB修复和V（D）J重组。
Ku is a complex of two proteins, Ku70 and Ku80, and functions as a heterodimer to bind DNA double-strand breaks (DSB) and activate DNA-dependent protein kinase. The role of the Ku70 subunit in DNA DSB repair, hypersensitivity to ionizing radiation, and V(D)J recombination was examined in mice that lack Ku70 (Ku70 −/−). Like Ku80 −/− mice, Ku70 −/− mice showed a profound deficiency in DNA DSB repair and were proportional dwarfs. Surprisingly, in contrast to Ku80−/− mice in which both T and B lymphocyte development were arrested at an early stage, lack of Ku70 was compatible with T cell receptor gene recombination and the development of mature CD4+CD8− and CD4−CD8+ T cells. Our data shows, for the first time, that Ku70 plays an essential role in DNA DSB repair, but is not required for TCR V(D)J recombination. These results suggest that distinct but overlapping repair pathways may mediate DNA DSB repair and V(D)J recombination.