Transcriptional regulation of human DNA repair genes following genotoxic stress: trigger mechanisms, inducible responses and genotoxic adaptation.
Transcriptional regulation of human DNA repair genes following genotoxic stress: trigger mechanisms, inducible responses and genotoxic adaptation.
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DOI：
10.1093/nar/gkt635
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发表时间：
2013-10
影响因子：
14.9
通讯作者：
Kaina B
中科院分区：
文献类型：
--
作者：
Christmann M;Kaina B
DNA修复是防御遗传毒性应激的第一道屏障。近年来，通过转录上调和翻译后修饰识别DNA损伤并激活DNA修复功能的机制成为研究热点。大多数DNA修复途径是复杂的，涉及许多蛋白质在离散的连续步骤中工作。因此，它们的平衡表达对于避免可能由过度碱基去除和DNA切割导致的错误修复是重要的。改善DNA修复需要一个微调的损伤识别系统和转录因子，以平衡的方式调节修复基因。基因毒性应激导致的DNA修复基因的转录上调被阻断转录的DNA损伤所抵消。因此，导致适应性反应的DNA修复诱导仅通过狭窄的剂量窗口可见。在这里，我们回顾了正常和癌细胞中DNA修复基因的转录调控，并描述了通过环境致癌物和抗癌药物的遗传毒性暴露后启动子激活的机制。迄今为止的数据表明，在啮齿动物和人类细胞中，25个DNA修复基因在遗传毒性应激后受到调控，但只有其中少数基因的机制、稳态调控和参与对遗传毒性应激的适应性反应的数据是可靠的。
DNA repair is the first barrier in the defense against genotoxic stress. In recent years, mechanisms that recognize DNA damage and activate DNA repair functions through transcriptional upregulation and post-translational modification were the focus of intensive research. Most DNA repair pathways are complex, involving many proteins working in discrete consecutive steps. Therefore, their balanced expression is important for avoiding erroneous repair that might result from excessive base removal and DNA cleavage. Amelioration of DNA repair requires both a fine-tuned system of lesion recognition and transcription factors that regulate repair genes in a balanced way. Transcriptional upregulation of DNA repair genes by genotoxic stress is counteracted by DNA damage that blocks transcription. Therefore, induction of DNA repair resulting in an adaptive response is only visible through a narrow window of dose. Here, we review transcriptional regulation of DNA repair genes in normal and cancer cells and describe mechanisms of promoter activation following genotoxic exposures through environmental carcinogens and anticancer drugs. The data available to date indicate that 25 DNA repair genes are subject to regulation following genotoxic stress in rodent and human cells, but for only a few of them, the data are solid as to the mechanism, homeostatic regulation and involvement in an adaptive response to genotoxic stress.
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影响因子：
5.3
作者：
Blattner, C;Kannouche, P;Herrlich, P
通讯作者：
Herrlich, P
影响因子：
6.4
作者：
Brozovic, A;Fritz, G;Kaina, B
通讯作者：
Kaina, B
影响因子：
3.6
作者：
Amundson, SA;Patterson, A;Fornace, AJ
通讯作者：
Fornace, AJ
影响因子：
8
作者：
Christmann, M;Tomicic, MT;Kaina, B
通讯作者：
Kaina, B
DOI：
10.1073/pnas.202485699
发表时间：
2002-10-01
影响因子：
11.1
作者：
Adimoolam, S;Ford, JM
通讯作者：
Ford, JM