4n-1 Is a "Sweet Spot" in DNA i-Motif Folding of 2′-Deoxycytidine Homopolymers
4n-1 Is a "Sweet Spot" in DNA i-Motif Folding of 2′-Deoxycytidine Homopolymers
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DOI：
10.1021/jacs.6b10117
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发表时间：
2017-04-05
影响因子：
15
通讯作者：
Burrows, Cynthia J.
中科院分区：
文献类型：
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作者：
Fleming, Aaron M.;Ding, Yun;Burrows, Cynthia J.
具有四个或更多2‘-脱氧胞苷(DC)核苷酸序列的DNA链有可能采用I基序折叠，通常在温和的酸性条件下。用五种不同的pH依赖方法对长度从10到30个核苷酸的DC同源寡核苷酸链进行分析，确定了链长度与稳定性之间的模式。从不折叠的DC(11)开始，随着最多4个核苷酸的加入，过渡pH(pH(T))随着链长的增加而增加，之后稳定性急剧下降，这一趋势重复到DC(27)。分析发现，长度为15、19、23和27个核苷酸(即4N-1)的DC(N)链具有pH(T)。值>；7.2和在pH 7.0时的热稳定性>；37℃。用胸苷核苷酸锁定I-基序环长的模型研究支持这一结论，即最稳定的DC(N)I-基序在三个环中的每个环中都有一个核苷酸和一个由偶数个碱基对组成的核心。根据DC(N)链的结果，从模型研究中识别的模式以长度为15、19、23和27的四个核苷酸的频率出现。这一观察结果使我们对DC(N)运行的人类基因组进行了询问。对人类基因组的检查表明，DC(N)Run在基因组的关键区域(启动子、UTRs和内含子)丰富，而在编码区和基因间隔区缺失，这些发现可能具有生物学意义。最后，通过链的长度调整I基序稳定性的能力可能被用于DNA支架、传感器、纳米技术和其他化学应用中的刺激反应应用：
Strand's of DNA with four or more contiguous runs of 2'-deoxycytidine (dC) nucleotides have the potential to adopt i-motif folds, generally under mildly acidic conditions. Analysis of dC homo-oligonucleotide strands ranging in length from 10 to 30 nucleotides by five different pH-dependent methods identified a pattern in strand length vs stability. Beginning with dC(11), which does not fold, the transition pH (pH(T)) increased with chain length with the addition of up to four nucleotides, after which the stability dramatically decreased, and the trend repeated this cycle up to dC(27). The analysis found dC(n) strands of length 15, 19, 23, and 27 nucleotides (i.e., 4n-1) to have pH(T). values >7.2 and thermal stabilities >37 degrees C at pH 7.0. Model studies using thymidine nucleotides to lock in i-motif loop lengths support, the conclusion that the most stable dC(n) i-motifs possess one nucleotide in each of the three loops and a core built of an even number of base pairs. The pattern identified from the model studies occurs with a frequency of four nucleotides at lengths of 15, 19, 23, and 27 in accordance with the results obtained for the dC(n) strands. This observation led us to interrogate the human genome for dC(n) runs. Inspection of the human genome indicates that dC(n) runs are enriched in critical regions of the genome (promoters, UTRs, and introns), while being depleted in coding and intergenic regions, and these findings may have biological implications. Lastly, the ability to tune i-motif stabilities by the length of the strand might be harnessed for stimulus-responsive applications in DNA scaffolds, sensors, nanotechnology, and other, chemical applications: