Ku70/80 gene expression and DNA-dependent protein kinase (DNA-PK) activity do not correlate with double-strand break (dsb) repair capacity and cellular radiosensitivity in normal human fibroblasts.

Ku70/80 gene expression and DNA-dependent protein kinase (DNA-PK) activity do not correlate with double-strand break (dsb) repair capacity and cellular radiosensitivity in normal human fibroblasts.
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KU70/80基因表达和DNA依赖性蛋白激酶(DNA-PK)活性与正常人成纤维细胞中的双链破裂(DSB)修复能力和细胞放射敏感性无关。

DOI:
10.1038/sj.bjc.6690166
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发表时间:
1999-03
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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--
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本文研究了11个正常人成纤维细胞株Ku 70和Ku 80基因的表达及DNA依赖性蛋白激酶(DNA-PK)的活性。研究的蛋白质是已知的一个双链断裂(dsb)修复复合物参与非同源重组的一部分,如被证明为互补组5-7的放射敏感性啮齿动物突变细胞系。本研究中使用的11个成纤维细胞系代表了正常人放射敏感性的典型谱,在3.5戈伊、SF 3.5戈伊剂量下测量的存活分数范围为0.03至0.28。细胞存活率的这些差异先前被证明与未修复的dsb的数量相关。我们发现,Ku 70和Ku 80基因的mRNA信号强度是相当相似的11个细胞系的调查。此外,在这些成纤维细胞系中,通过下拉试验测定的DNA-PK活性相当恒定。尽管细胞存活与dsb修复能力之间存在相关性,但在测试的正常人成纤维细胞系中,dsb修复能力与DNA-PK活性之间不存在相关性。显然,在这方面,其他蛋白质/途径似乎更相关。© 1999癌症研究运动
The expression of the Ku70 and Ku80 genes as well as the activity of the DNA-dependent protein kinase (DNA-PK) were studied in 11 normal human fibroblast lines. The proteins studied are known to be part of a double-strand break (dsb) repair complex involved in non-homologous recombination, as was demonstrated for the radiosensitive rodent mutant cell lines of the complementation groups 5–7. The 11 fibroblast lines used in this study represent a typical spectrum of normal human radiosensitivity with the surviving fraction measured for a dose of 3.5 Gy, SF3.5 Gy, ranging from 0.03 to 0.28. These differences in cell survival were previously shown to correlate with the number of non-repaired dsbs. We found that the mRNA signal intensities of both Ku70 and Ku80 genes were fairly similar for the 11 cell lines investigated. In addition, the DNA-PK activity determined by the pulldown assay was fairly constant in these fibroblast lines. Despite the correlation between cell survival and dsb repair capacity, there was no correlation between dsb repair capacity and DNA-PK activity in the tested normal human fibroblast lines. Obviously, in this respect, other proteins/pathways appear to be more relevant. © 1999 Cancer Research Campaign
DOI: 10.1016/s0968-0004(00)89090-8
发表时间: 1995-10-01
影响因子: 13.8
作者:
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通讯作者: JEGGO, PA
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发表时间: 1992-11-01
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发表时间: 1996-09-01
影响因子: 2.6
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发表时间: 1996-05-01
影响因子: 5.4
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通讯作者: deVillartay, JP