Unique Length-Dependent Biophysical Properties of Repetitive DNA.
Unique Length-Dependent Biophysical Properties of Repetitive DNA.
复制标题
重复DNA的独特长度依赖性生物物理特性。
DOI：
10.1021/acs.jpcb.6b00927
复制
发表时间：
2016-05-12
期刊：
影响因子：
--
通讯作者：
Delaney S
中科院分区：
文献类型：
--
作者：
Huang J;Delaney S
三核苷酸重复序列（TNR）的扩增是几种神经系统疾病的分子特征。TNR序列的非正则结构的形成被认为是膨胀机制的一部分。此外，已知扩增的倾向随着重复长度而增加。在这项工作中，我们使用量热法来描述由TNR序列（CAG）n和（CTG）n形成的非典型茎环发夹的热力学参数（ΔH，TΔS和ΔG），以及典型的（CAG）n/（CTG）n双链体，n = 6-14。使用热力学循环，我们计算了描述从非典型茎环发夹到典型双链体的转化过程的相同热力学参数。除了这些热力学分析，我们还使用光谱技术来确定非正则结构转化为双链体的速率，以及描述这一过程的活化焓ΔH。我们报道了展开茎环（CTG）n和（CAG）n发夹的热力学参数，沿着发夹到双链体转化的热力学和动力学性质，不成比例地对应于长度的增加，而是显示出一种独特的模式，取决于序列是否具有偶数或奇数的重复。
Expansion of a trinucleotide repeat (TNR) sequence is the molecular signature of several neurological disorders. Formation of non-canonical structures by the TNR sequence is proposed to contribute to the expansion mechanism. Furthermore, it is known that the propensity for expansion increases with repeat length. In this work we use calorimetry to describe the thermodynamic parameters (ΔH, TΔS, and ΔG) of the non-canonical stem-loop hairpins formed by the TNR sequences (CAG)n and (CTG)n, and also the canonical (CAG)n/(CTG)n duplexes, for n = 6–14. Using a thermodynamic cycle, we calculated the same thermodynamic parameters describing the process of converting from non-canonical stem-loop hairpins to canonical duplex. In addition to these thermodynamic analyses, we used spectroscopic techniques to determine the rate at which the non-canonical structures convert to duplex, and the activation enthalpy ΔH‡ describing this process. We report that the thermodynamic parameters of unfolding the stem-loop (CTG)n and (CAG)n hairpins, along with the thermodynamic and kinetic properties of hairpin to duplex conversion, do not proportionally corresponding to the increase of length, but rather show a unique pattern that depends on whether the sequence has an even or odd number of repeats.