Defective embryonic neurogenesis in Ku-deficient but not DNA-dependent protein kinase catalytic subunit-deficient mice
Defective embryonic neurogenesis in Ku-deficient but not DNA-dependent protein kinase catalytic subunit-deficient mice
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DOI：
10.1073/pnas.97.6.2668
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发表时间：
2000-03-14
影响因子：
11.1
通讯作者：
Alt, FW
中科院分区：
文献类型：
--
作者：
Gu, YS;Sekiguchi, J;Alt, FW
哺乳动物非同源DNA末端连接使用Ku 70、Ku 80。DNA依赖性蛋白激酶催化亚基（DNA-PKcs）、XRCC 4和DNA连接酶IV（Lig 4）。在此，我们表明Ku 70和Ku 80缺陷，但不是DNA-PKcs缺陷导致小鼠胚胎神经元发育中的死亡显着增加。Ku缺陷表型在性质上类似于XRCC 4和Lig 4缺陷相关的表型，但不那么严重。DNA-PKcs缺陷型胚胎中神经元死亡表型的缺乏以及Ku缺陷型相对于XRCC 4或Lig 4缺陷型胚胎的较温和表型与这些突变背景中残余末端连接的相对泄漏相关，如通过V（D）J重组末端连接测定所测定的。我们的结论是神经系统的正常发育依赖于四个进化上保守的非同源DNA末端连接因子。
Mammalian nonhomologous DNA end joining employs Ku70, Ku80. DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4 and DNA ligase IV (Lig4). Herein, we show that Ku70 and Ku80 deficiency but not DNA-PKcs deficiency results in dramatically increased death of developing embryonic neurons in mice. The Ku-deficient phenotype is qualitatively similar to, but less severe than, that associated with XRCC4 and Lig4 deficiency. The lack of a neuronal death phenotype in DNA-PKcs-deficient embryos and the milder phenotype of Ku-deficient versus XRCC4- or Lig4-deficient embryos correlate with relative leakiness of residual end joining in these mutant backgrounds as assayed by a V(D)J recombination end joining assay. We conclude that normal development of the nervous system depends on the four evolutionarily conserved nonhomologous DNA end joining factors.