Effects of Adenine Methylation on the Structure and Thermodynamic Stability of a DNA Minidumbbell.
Effects of Adenine Methylation on the Structure and Thermodynamic Stability of a DNA Minidumbbell.
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DOI：
10.3390/ijms22073633
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发表时间：
2021-03-31
影响因子：
5.6
通讯作者：
Guo P
中科院分区：
文献类型：
--
作者：
Wan L;Lam SL;Lee HK;Guo P
DNA甲基化是原核生物和真核生物中普遍存在的调控性修饰。N1-甲基腺嘌呤（m1A）和N6-甲基腺嘌呤（m6 A）被发现能够通过干扰沃森-克里克碱基配对来改变DNA结构。然而，很少有人知道它们对非B DNA结构的影响，这与遗传不稳定性有关。在这项工作中，我们研究了m1A和m6 A对新报道的由两个TTTA四核苷酸重复形成的DNA minidumbbell的结构和热力学稳定性的影响。核磁共振光谱研究结果表明，m1A和m6 A分别有利于形成T·m1A和T·m6 A Hoogsteen碱基对。更有趣的是，m1A和m6 A修饰分别对DNA微型哑铃产生稳定和不稳定作用。这项工作提供了新的生物物理学的见解腺嘌呤甲基化对DNA的结构和热力学稳定性的影响。
DNA methylation is a prevalent regulatory modification in prokaryotes and eukaryotes. N1-methyladenine (m1A) and N6-methyladenine (m6A) have been found to be capable of altering DNA structures via disturbing Watson–Crick base pairing. However, little has been known about their influences on non-B DNA structures, which are associated with genetic instabilities. In this work, we investigated the effects of m1A and m6A on both the structure and thermodynamic stability of a newly reported DNA minidumbbell formed by two TTTA tetranucleotide repeats. As revealed by the results of nuclear magnetic resonance spectroscopic studies, both m1A and m6A favored the formation of a T·m1A and T·m6A Hoogsteen base pair, respectively. More intriguingly, the m1A and m6A modifications brought about stabilization and destabilization effects on the DNA minidumbbell, respectively. This work provides new biophysical insights into the effects of adenine methylation on the structure and thermodynamic stability of DNA.