DNA topology


DNA topology is an essential interplay between the spatial configuration of the genetic material and its accessibility to major DNA structural transactions. In most organisms, DNA is maintained in a homeostatically-underwound, that is, negatively supercoiled, state, and presents transient supercoiling in both the positive and negative directions due to processes like replication and transcription. In turn, torsional stress is relieved by the coiling of the DNA helix around itself, which requires bending deformation and contributes to nucleoid structure, and by the opening of the double helix, which provides an underlying regulatory switch for transcription/replication initiation. Besides, DNA supercoiling influences gene regulation by altering both the global and the local structure of the helix. Recently reviewed at Noy et al. Biophys Rev (2016).

Interference between triplex and protein binding to distal sites on supercoiled DNA

This paper, which shows that supercoiled DNA plectonemes promote nonspecific protein-DNA interactions building unexpected closed DNA loops, was published and highlighted at Noy, Maxell and Harris Biophys J (2017). This illustrative image was placed at the slider of the Biophysical Journal’s main webpage.

Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation

Multi-scale cooperation with the groups of Ard Louis, John Doye (oxDNA) and Craig Benham (SIDD) for understanding the origins of DNA double-strand separation. The main conclusion was that there was a physical coupling across the whole minicircles so the probability to melt is nojust dependent of local sequence but depends of the whole topological domain. Sutthibutpong et al NAR (2016).

WrLINE, an improved molecular contour for measuring writhe in atomistic supercoiled DNA

Besides, toc Thana Sutthibutpong and I have designed a center-line called WrLINE for measuring the degree of supercoiling in atomistic DNA, that is capable of mirroring low-resolution experimental measurements, to facilitate comparisons between the two. (Sutthibutpong, Harris and Noy, JCTC 2015)