Microsatellite instability induced, by hydrogen peroxide in Escherichia coli
Microsatellite instability induced, by hydrogen peroxide in Escherichia coli
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DOI：
10.1016/s0027-5107(99)00206-7
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发表时间：
2000-02-14
影响因子：
2.3
通讯作者：
Loeb, LA
中科院分区：
文献类型：
--
作者：
Jackson, AL;Loeb, LA
活性氧对DNA的损伤可能是需氧生物内源性诱变的重要来源。利用微卫星不稳定性的选择性分析方法，在E.通过调用，我们已经询问了内源性氧化诱变是否会导致遗传不稳定性。内含子序列和编码区内重复序列的不稳定性是人类癌症遗传不稳定性的标志。我们证明了E.大肠杆菌对低水平的过氧化氢的耐受性增加了二核苷酸重复序列内的扩增和缺失的频率。对突变体克隆中的重复序列和侧翼非重复区域进行测序，证明了重复序列改变的高度特异性。所有的183个突变体测序显示微卫星重复内的移码突变，和没有碱基取代或移码突变发生在侧翼的非重复序列。我们推测，内源性氧化损伤DNA可以增加DNA复制或修复合成过程中发生的链滑移中间体的频率，并有助于基因组的不稳定性。(C)2000 Elsevier Science B.V.保留所有权利。
Damage to DNA by reactive oxygen species may be a significant source of endogenous mutagenesis in aerobic organisms. Using a selective assay for microsatellite instability in E. call, we have asked whether endogenous oxidative mutagenesis can contribute to genetic instability. Instability of repetitive sequences, both in intronic sequences and within coding regions, is a hallmark of genetic instability in human cancers. We demonstrate that exposure of E. coli to low levels of hydrogen peroxide increases the frequency of expansions and deletions within dinucleotide repetitive sequences. Sequencing of the repetitive sequences and flanking non-repetitive regions in mutant clones demonstrated the high specificity for alterations with the repeats. All of the 183 mutants sequenced displayed frameshift alterations within the microsatellite repeats, and no base substitutions or frameshift mutations occurred within the flanking non-repetitive sequences. We hypothesize that endogenous oxidative damage to DNA can increase the frequency of strand slippage intermediates occurring during DNA replication or repair synthesis, and contribute to genomic instability. (C) 2000 Elsevier Science B.V. All rights reserved.