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Investigating site-selection mechanisms of retroviral integration in supercoiled DNA braids
Journal of The Royal Society Interface ( IF 3.9 ) Pub Date : 2021-08-25 , DOI: 10.1098/rsif.2021.0229
G Forte 1, 2 , D Michieletto 1, 2 , D Marenduzzo 1 , E Orlandini 3
Affiliation  

We theoretically study the integration of short viral DNA in a DNA braid made up by two entwined double-stranded DNA molecules. We show that the statistics of single integration events substantially differ in the straight and buckled, or plectonemic, phase of the braid and are more likely in the latter. We further discover that integration is most likely close to plectoneme tips, where the larger bending energy helps overcome the associated energy barrier and that successive integration events are spatio-temporally correlated, suggesting a potential mechanistic explanation of clustered integration sites in host genomes. The braid geometry we consider provides a novel experimental set-up to quantify integration in a supercoiled substrate in vitro, and to better understand the role of double-stranded DNA topology during this process.



中文翻译:

研究超螺旋 DNA 辫子中逆转录病毒整合的位点选择机制

我们从理论上研究了短病毒 DNA 在由两个缠绕的双链 DNA 分子组成的 DNA 编织物中的整合。我们表明,单个积分事件的统计数据在辫子的直线和弯曲阶段或 plectonemic 阶段大不相同,并且在后者中更有可能。我们进一步发现整合最有可能接近 plectoneme 提示,其中较大的弯曲能量有助于克服相关的能量障碍,并且连续的整合事件是时空相关的,这表明对宿主基因组中的聚集整合位点的潜在机械解释。我们考虑的编织几何形状提供了一种新颖的实验装置来量化体外超螺旋基底中的整合,并更好地了解双链 DNA 拓扑在此过程中的作用。

更新日期:2021-08-25
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