Biophysical Society Thematic Meeting| Santa Cruz 2018

Genome Biophysics: Integrating Genomics and Biophysics to Understand Structural and Functional Aspects of Genomes

Poster Abstracts

14-POS Board 14 Regulatory Role of DNA Sequence in Mechanics of DNA Supercoiling Transitions Anna Reymer 1 1 University of Gothenburg, Chemistry and Molecular Biology, Gothenburg, V ä stra Götalands l ä n, Sweden Ability of DNA to dynamically change its superhelical state is central to many biological functions, including regulation of gene expression, repair, and packaging in the cell. To address conformational mechanics of DNA during supercoiling transitions we designed a new molecular modelling tool, which can be used in complement with standard all-atom molecular dynamics software. The tool controls the torsional state of DNA between any two base pairs, without restricting any other DNA helical parameter. The tool can be applied to DNA molecules of any length and curvature, alone or in complex with other molecules. This allows for the first time to study DNA in conditions resembling its in vivo state, where DNA’s topology is substantially restricted. We applied the tool to a number of linear DNA molecules, including several with methylated cytosine bases, changing their superhelical density from -0.2 to +0.2, which corresponds to under- or overwinding by 6 degrees per base pair step. DNA’s response to the torsional stress appears discontinuous - certain dinucleotides are capable of absorbing most of the torsional stress. These "twist-capacitor" dinucleotides, as we call them, modify their twist through coupled conformational changes in DNA backbone. This allows the rest of DNA to remain close to canonical B-form, despite the overall torsional stress. We observe similar trends also in methylated DNA sequences. Overall cytosine methylation stiffens the DNA molecules. But the effect is strongly modulated by the surrounding sequence, where the epigenetic mark could hinder either under- or overwinding molecular transitions. These findings constitute a new aspect of how DNA sequence contributes to biological regulation.

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