STRUCTURE OF AN ADENINE.CYTOSINE BASE PAIR IN DNA AND ITS IMPLICATIONS FOR MISMATCH REPAIR
STRUCTURE OF AN ADENINE.CYTOSINE BASE PAIR IN DNA AND ITS IMPLICATIONS FOR MISMATCH REPAIR
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DOI：
10.1038/320552a0
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发表时间：
1986-04-10
期刊：
影响因子：
64.8
通讯作者：
KENNARD, O
中科院分区：
文献类型：
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作者：
HUNTER, WN;BROWN, T;KENNARD, O
突变途径依赖于在DNA双螺旋中引入变化。这可以通过在复制或基因重组过程中掺入非互补碱基来实现1，2，导致替换突变。体内研究3 - 7表明，大多数碱基对错配的组合可以容纳在DNA双螺旋中，尽管效率不同。复制的保真度需要通过校正酶和复制后错配修复系统识别和切除错配碱基。切除率随错配类型而变化，并且有证据表明这些受相邻序列的性质影响8，9。然而，关于错配的分子结构及其对DNA双螺旋的影响的实验信息很少。我们最近已经确定了几个DNA片段的晶体结构与鸟嘌呤o胸腺嘧啶和腺嘌呤o鸟嘌呤错配在一个完整的B-DNA螺旋，现在报告的性质之间的碱基配对腺嘌呤和胞嘧啶的同晶片段。在本研究中发现的碱基对是新颖的，我们相信以前没有被证明。我们的研究结果表明，错配的酶识别可能发生在碱基对的水平，修复的效率可以与结构特征。
Mutational pathways rely on introducing changes in the DNA double helix. This may be achieved by the incorporation of a noncomplementary base on replication or during genetic recombination1,2, leading to substitution mutation.In vivostudies3–7have shown that most combinations of base-pair mismatches can be accommodated in the DNA double helix, albeit with varying efficiencies. Fidelity of replication requires the recognition and excision of mismatched bases by proofreading enzymes and post-replicative mismatch repair systems. Rates of excision vary with the type of mismatch and there is some evidence that these are influenced by the nature of the neighbouring sequences8,9. However, there is little experimental information about the molecular structure of mismatches and their effect on the DNA double helix. We have recently determined the crystal structures of several DNA fragments with guanine o thymine and adenine o guanine mismatches in a full turn of a B-DNA helix and now report the nature of the base pairing between adenine and cytosine in an isomorphous fragment. The base pair found in the present study is novel and we believe has not previously been demonstrated. Our results suggest that the enzymatic recognition of mismatches is likely to occur at the level of the base pairs and that the efficiency of repair can be correlated with structural features.