{"title":"Supercoiled DNA Minicircles under Double-strand Breaks","authors":"Ye-Peng Qiao, Chun-Lai Ren","doi":"10.1007/s10118-024-3106-8","DOIUrl":null,"url":null,"abstract":"<p>Understanding how supercoiled DNA releases intramolecular stress is essential for its functional realization. However, the molecular mechanism underlying the relaxation process remains insufficiently explored. Here we employed MD simulations based on the oxDNA2 model to investigate the relaxation process of a 336-base pair supercoiled minicircular DNA under double-strand breaks with two fixed endpoints. Our simulations show that the conformational changes in the DNA occur continuously, with intramolecular stress release happening abruptly only when the DNA chain traverses the breakage site. The relaxation process is influenced not only by the separation distance between the fixed ends but also their angle. Importantly, we observe an inhibitory effect on the relaxation characterized by small angles, where short terminal loops impede DNA conformational adjustments, preserving the supercoiled structure. These findings elucidate the intricate interplay between DNA conformational change, DNA motion and intramolecular stress release, shedding light on the mechanisms governing the relaxation of supercoiled DNA at the molecular level.</p>","PeriodicalId":517,"journal":{"name":"Chinese Journal of Polymer Science","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Polymer Science","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s10118-024-3106-8","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"POLYMER SCIENCE","Score":null,"Total":0}
引用次数: 0
Abstract
Understanding how supercoiled DNA releases intramolecular stress is essential for its functional realization. However, the molecular mechanism underlying the relaxation process remains insufficiently explored. Here we employed MD simulations based on the oxDNA2 model to investigate the relaxation process of a 336-base pair supercoiled minicircular DNA under double-strand breaks with two fixed endpoints. Our simulations show that the conformational changes in the DNA occur continuously, with intramolecular stress release happening abruptly only when the DNA chain traverses the breakage site. The relaxation process is influenced not only by the separation distance between the fixed ends but also their angle. Importantly, we observe an inhibitory effect on the relaxation characterized by small angles, where short terminal loops impede DNA conformational adjustments, preserving the supercoiled structure. These findings elucidate the intricate interplay between DNA conformational change, DNA motion and intramolecular stress release, shedding light on the mechanisms governing the relaxation of supercoiled DNA at the molecular level.
了解超螺旋 DNA 如何释放分子内应力对实现其功能至关重要。然而,对弛豫过程的分子机制仍然缺乏足够的探索。在此,我们采用基于 oxDNA2 模型的 MD 模拟,研究了 336 碱基对超螺旋小圆 DNA 在双链断裂(有两个固定端点)情况下的松弛过程。模拟结果表明,DNA 的构象变化是连续发生的,只有当 DNA 链穿过断裂点时,分子内应力才会突然释放。弛豫过程不仅受固定端点之间分离距离的影响,还受其角度的影响。重要的是,我们观察到小角度对松弛的抑制作用,短末端环阻碍了 DNA 的构象调整,从而保持了超卷曲结构。这些发现阐明了 DNA 构象变化、DNA 运动和分子内应力释放之间错综复杂的相互作用,揭示了超螺旋 DNA 在分子水平上的松弛机制。
期刊介绍:
Chinese Journal of Polymer Science (CJPS) is a monthly journal published in English and sponsored by the Chinese Chemical Society and the Institute of Chemistry, Chinese Academy of Sciences. CJPS is edited by a distinguished Editorial Board headed by Professor Qi-Feng Zhou and supported by an International Advisory Board in which many famous active polymer scientists all over the world are included. The journal was first published in 1983 under the title Polymer Communications and has the current name since 1985.
CJPS is a peer-reviewed journal dedicated to the timely publication of original research ideas and results in the field of polymer science. The issues may carry regular papers, rapid communications and notes as well as feature articles. As a leading polymer journal in China published in English, CJPS reflects the new achievements obtained in various laboratories of China, CJPS also includes papers submitted by scientists of different countries and regions outside of China, reflecting the international nature of the journal.