Gene transcription by an RNA polymerase (RNAP) enzyme requires that double-stranded DNA be locally and transiently opened, which results in an increase of DNA supercoiling downstream of the RNAP and a decrease of supercoiling upstream of it. When the DNA is initially torsionally relaxed and the RNAP experiences sufficiently large rotational drag, these variations lead to positively supercoiled plectonemes ahead of the RNAPs and negatively supercoiled ones behind it, a feature known as “twin supercoiled domain” (TSD). This work aims at deciphering into some more detail the torsional dynamics of circular DNA molecules being transcribed by RNAP enzymes. To this end, we performed Brownian dynamics simulations with a specially designed coarse-grained model. Depending on the superhelical density of the DNA molecule and the ratio of RNAP’s twist injection rate and rotational relaxation speed, simulations reveal a rich panel of behaviors, which sometimes differ markedly from the crude TSD picture. In particular, for sufficiently slow rotational relaxation speed, positively supercoiled plectonemes never form ahead of an RNAP that transcribes a DNA molecule with physiological negative supercoiling. Rather, negatively supercoiled plectonemes form almost periodically at the upstream side of the RNAP and grow up to a certain length before detaching from the RNAP and destabilizing rapidly. The extent to which topological barriers hinder the dynamics of TSDs is also discussed.

中文翻译：

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转录 RNA 聚合酶：双超螺旋结构域的动力学


RNA 聚合酶 （RNAP） 酶的基因转录要求双链 DNA 局部和瞬时开放，这导致 RNAP 下游 DNA 超螺旋的增加和上游超螺旋的减少。当 DNA 最初扭转松弛并且 RNAP 经历足够大的旋转阻力时，这些变化导致 RNAP 前面的正超螺旋 lectonemes 和它后面的负超螺旋 plectonemes，这一特征称为“双超螺旋结构域”（TSD）。这项工作旨在更详细地破译 RNAP 酶转录的环状 DNA 分子的扭转动力学。为此，我们使用专门设计的粗粒度模型进行了布朗动力学模拟。根据 DNA 分子的超螺旋密度以及 RNAP 的扭曲注射速率和旋转弛豫速度的比率，模拟揭示了一组丰富的行为，这些行为有时与粗略的 TSD 图片明显不同。特别是，对于足够慢的旋转弛豫速度，正超螺旋的 plectonemes 永远不会在转录具有生理负超螺旋的 DNA 分子的 RNAP 之前形成。相反，负超螺旋的 plectonemes 几乎周期性地在 RNAP 的上游侧形成，并在从 RNAP 分离并迅速不稳定之前长到一定长度。还讨论了拓扑障碍在多大程度上阻碍了 TSD 的动力学。