Interactions among the Escherichia coli mutT, mutM, and mutY damage prevention pathways
Interactions among the Escherichia coli mutT, mutM, and mutY damage prevention pathways
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DOI：
10.1016/s1568-7864(02)00193-3
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发表时间：
2003-02-03
期刊：
影响因子：
3.8
通讯作者：
Schaaper, RM
中科院分区：
文献类型：
--
作者：
Fowler, RG;White, SJ;Schaaper, RM
我们已经详细研究了大肠杆菌mutT，mutM和mutY错误预防系统之间的相互作用。这些系统共同保护细胞免受氧化应激产物8-氧代鸟嘌呤（8-oxoG）的影响，8-oxoG是一种具有模糊碱基配对特性的碱基类似物，在DNA合成期间与A或C配对。mutT突变株表现出A.T → C.G颠换的特异性增加，而mutM和mutY突变株表现出G. C → T. A的特异性增加。为了更详细地研究导致A.T --> C.G和G. C--> T. A颠换的各种突变中间体的体内加工，我们分析了含有这些增变等位基因的所有可能组合的菌株中定义的A.T --> C.G和G. C--> T. A事件。我们报告三个主要发现。首先，我们没有发现mutT等位基因在mut（+）、mutM、mutY或mutMmutY背景下显著增加G. C--> T. A颠换的证据。我们将该结果解释为，相对于相对模板A的掺入，相对模板C的8-oxodGTP的掺入可能不频繁。其次，我们发现，mutT诱导的A.T -> C.G颠换在携带mutY和mutMmutY缺陷的菌株中显著减少，这表明8-oxoG当存在于DNA中时，优先与dATP错配。第三，mutY和mutMmutY缺陷也会减少muT（+）背景下的A.T --> C.G颠换，这表明即使在功能性MutT蛋白存在的情况下，A.T --> C.G颠换仍然可能是由8-oxodGTP错误掺入引起的。(C)2002 Elsevier Science B. V.保留所有权利。
We have investigated in detail the interactions between the Escherichia coli mutT, mutM, and mutY error-prevention systems. Jointly, these systems protect the cell against the effects of the oxidative stress product, 8-oxoguanine (8-oxoG), a base analog with ambiguous base-pairing properties, pairing with either A or C during DNA synthesis. mutT mutator strains display a specific increase in A.T --> C.G transversions, while mutM and mutY mutator strains show specific G.C --> T.A increases. To study in more detail the in vivo processing of the various mutational intermediates leading to A.T --> C.G and G.C --> T.A transversions, we analyzed defined A.T --> C.G and G.C --> T.A events in strains containing all possible combinations of these mutator alleles. We report three major findings. First, we do not find evidence that the mutT allele significantly increases G.C --> T.A transversions in either mut(+), mutM, mutY or mutMmutY backgrounds. We interpret this result to indicate that incorporation of 8-oxodGTP opposite template C may not be frequent relative to incorporation opposite template A. Second, we show that mutT-induced A.T --> C.G transversions are significantly reduced in strains carrying mutY and mutMmutY deficiencies suggesting that 8-oxoG, when present in DNA, preferentially mispairs with dATP. Third, the mutY and mutMmutY deficiencies also decrease A.T --> C.G transversions in the muT(+) background, suggesting that, even in the presence of functional MutT protein, A.T --> C.G transversions may still result from 8-oxodGTP misincorporation. (C) 2002 Elsevier Science B.V. All rights reserved.