Context dependence of trinucleotide repeat structures.
Context dependence of trinucleotide repeat structures.
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DOI：
10.1021/bi902043u
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发表时间：
2010-04-13
期刊：
影响因子：
2.9
通讯作者：
Petty JT
中科院分区：
文献类型：
--
作者：
Degtyareva NN;Barber CA;Sengupta B;Petty JT
DNA的长重复序列及其相关的二级结构控制着一类重要神经疾病的发展和严重程度。利用碱基堆积对荧光量子产率的影响，腺嘌呤的2-氨基嘌呤取代先前显示了分离的(CAG)8序列的茎中的隔离碱基和环中暴露的碱基。本研究评估了被纳入双链的(CAG)8，因为这个三向连接是导致DNA复制和修复过程中重复扩张的中间产物的相关模型。从能量的角度来看，热诱导变性表明双臂决定了稳定性，重复序列的二级结构被破坏。2-氨基嘌呤探针碱基暴露在整个结构中的取代反应，并得出了关于二级结构的两个结论。首先，(CAG)8的中心区域比单链DNA更容易暴露于溶剂中，这表明重复序列中的发夹形成被破坏。其次，在从双链到(CAG)8的转变中，碱基堆积变得妥协，导致连接处的碱基最类似于单链DNA。因此，开放的(CAG)8环和手臂中暴露的碱基表明，链连接深刻地影响三向连接内的重复序列。
Long repeated sequences of DNA and their associated secondary structure govern the development and severity of a significant class of neurological diseases. Utilizing the effect of base stacking on fluorescence quantum yield, 2-aminopurine substitutions for adenine previously demonstrated sequestered bases in the stem and exposed bases in the loop for an isolated (CAG)8 sequence. The present studies evaluate (CAG)8 that is incorporated into a duplex, as this three-way junction is a relevant model for intermediates that lead to repeat expansion during DNA replication and repair. From an energetic perspective, thermally-induced denaturation indicates that the duplex arms dictate stability and that secondary structure of the repeated sequence is disrupted. Substitutions with 2-aminopurine probe base exposure throughout this structure, and two conclusions about secondary structure are derived. First, the central region of (CAG)8 is more solvent-exposed than single-stranded DNA, which suggests that hairpin formation in the repeated sequence is disrupted. Second, base stacking becomes compromised in the transition from duplex to (CAG)8, resulting in bases that are most similar to single-stranded DNA at the junction. Thus, an open (CAG)8 loop and exposed bases in the arms indicate that the strand junction profoundly influences repeated sequences within three-way junctions.
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