Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats.
Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats.
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DOI：
10.1093/nar/gki716
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发表时间：
2005
影响因子：
14.9
通讯作者：
Mergny, JL
中科院分区：
文献类型：
--
作者：
Amrane, S;Saccà, B;Mills, M;Chauhan, M;Klump, HH;Mergny, JL
三核苷酸重复与许多衰弱性疾病如肌强直性营养不良有关。使用生物物理[紫外吸收，圆二色性和差示扫描量热法（DSC）]和生化方法（非变性凝胶电泳和酶印迹）相结合的方法分析了12至75个碱基长（CTG）n寡脱氧核苷酸。所有的低聚物在接近生理条件下形成稳定的分子内结构，熔融温度对低聚物长度的依赖性较弱。通过紫外熔融和量热实验对变性过程进行热力学分析，揭示了依赖模型（紫外熔融）和不依赖模型（量热）实验得出的焓值之间存在前所未有的长度相关差异。对Arrhenius图和DSC谱图的分析也得到了非零摩尔热容变化的证据。这种行为是在分子内“分支发夹”模型的框架内分析的，在这个模型中，长CTG低聚物不会折叠成简单的长发夹干分子内结构，而是允许形成几个不稳定的独立折叠单元。我们证明，对于12到25个CTG重复序列，形成了一个具有两个环的分子内结构，我们将其称为“双发夹”。在CAG低聚物中也发现了类似的结果，表明这一观察结果可能适用于各种含三核苷酸重复序列。
Trinucleotide repeats are involved in a number of debilitating diseases such as myotonic dystrophy. Twelve to seventy-five base-long (CTG)n oligodeoxynucleotides were analysed using a combination of biophysical [UV-absorbance, circular dichroism and differential scanning calorimetry (DSC)] and biochemical methods (non-denaturing gel electrophoresis and enzymatic footprinting). All oligomers formed stable intramolecular structures under near physiological conditions with a melting temperature that was only weakly dependent on oligomer length. Thermodynamic analysis of the denaturation process by UV-melting and calorimetric experiments revealed an unprecedented length-dependent discrepancy between the enthalpy values deduced from model-dependent (UV-melting) and model-independent (calorimetry) experiments. Evidence for non-zero molar heat capacity changes was also derived from the analysis of the Arrhenius plots and DSC profiles. Such behaviour is analysed in the framework of an intramolecular ‘branched-hairpin’ model, in which long CTG oligomers do not fold into a simple long hairpin–stem intramolecular structure, but allow the formation of several independent folding units of unequal stability. We demonstrate that, for sequences ranging from 12 to 25 CTG repeats, an intramolecular structure with two loops is formed which we will call ‘bis-hairpin’. Similar results were also found for CAG oligomers, suggesting that this observation may be extended to various trinucleotide repeats-containing sequences.
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DOI：
10.1073/pnas.92.11.5199
发表时间：
1995-05-23
影响因子：
11.1
作者：
CHEN, XA;MARIAPPAN, SVS;GUPTA, G
通讯作者：
GUPTA, G
影响因子：
2.9
作者：
Chastain, PD;Eichler, EE;Sinden, RR
通讯作者：
Sinden, RR
影响因子：
14.9
作者：
Mariappan, SVS;Garcia, AE;Gupta, G
通讯作者：
Gupta, G
影响因子：
56.9
作者：
Liquori, CL;Ricker, K;Ranum, LPW
通讯作者：
Ranum, LPW
DOI：
10.1016/s0027-5107(02)00190-2
发表时间：
2002-10-31
影响因子：
2.3
作者：
Hashem, VI;Sinden, RR
通讯作者：
Sinden, RR