Influence of DNA sequence on the structure of minicircles under torsional stress.
Influence of DNA sequence on the structure of minicircles under torsional stress.
复制标题
DNA 序列对扭转应力下小环结构的影响。
DOI：
10.1093/nar/gkx516
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发表时间：
2017
影响因子：
14.9
通讯作者：
Pettitt,BMontgomery
中科院分区：
文献类型：
--
作者：
Wang,Qian;Irobalieva,RossitzaN;Chiu,Wah;Schmid,MichaelF;Fogg,JonathanM;Zechiedrich,Lynn;Pettitt,BMontgomery
在不同水平的扭转应力下，DNA构象分布的序列依赖性是一个重要的未解决的问题。结合理论和粗粒度的模拟表明，DNA序列和结构的相关性，由于拓扑结构的限制，一个圆的主要因素，决定了一个336 bp的DNA微环在扭转应力下的三维结构。我们发现，DNA微环拓扑异构体可以有多个弯曲的位置在高的扭转应力和这些急剧弯曲的位置是由序列，并通过一个积极的机械相关性沿着序列。我们表明，模拟和理论是能够提供特定序列的信息，通过冷冻电子断层扫描（cryo-ET）观察到的个别DNA微环。我们提供了DNA微环的序列特异性cryo-ET断层图像拟合，在几何特征内登记序列。我们的研究结果表明，微环在扭转应力下的构象分布是可以设计的，这对于利用微环DNA进行基因治疗具有重要意义。
The sequence dependence of the conformational distribution of DNA under various levels of torsional stress is an important unsolved problem. Combining theory and coarse-grained simulations shows that the DNA sequence and a structural correlation due to topology constraints of a circle are the main factors that dictate the 3D structure of a 336 bp DNA minicircle under torsional stress. We found that DNA minicircle topoisomers can have multiple bend locations under high torsional stress and that the positions of these sharp bends are determined by the sequence, and by a positive mechanical correlation along the sequence. We showed that simulations and theory are able to provide sequence-specific information about individual DNA minicircles observed by cryo-electron tomography (cryo-ET). We provided a sequence-specific cryo-ET tomogram fitting of DNA minicircles, registering the sequence within the geometric features. Our results indicate that the conformational distribution of minicircles under torsional stress can be designed, which has important implications for using minicircle DNA for gene therapy.