Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

Polymorphism within Complex DNA Topologies

The DNA double helix is an iconic structure that is universally recognised, and which has become a popularised image that signifies scientific discovery and understanding. However, I will argue that this media representation of the double helix is a gratuitous oversimplification of the true nature of the genetic material as found within the cell, even for prokaryotic genomes. This is because cellular DNA is both decorated by numerous DNA binding protein and also supercoiled, with the result that it possesses complex topologies and an abundance of polymorphic forms that are essential for gene regulation.

We use atomistic molecular dynamics simulations of small DNA circles to observe and characterise how supercoiling affects DNA structure and dynamics at both the local and global levels. We show that a diverse assortment of topologies and non-canonical structures can be induced, which enhances the informational capacity of the DNA beyond that encoded by its chemical sequence, especially since the precise nature of these disruptions is frequently time dependent. Changes in DNA structure also effect molecular recognition, which is the central mechanism for information transfer and signalling in biomolecular systems. Based on insight from our computer simulations, we speculate on the biological consequences of DNA polymorphism, taking inspiration from the literature.

    Bates A. D., Noy A., Piperakis M. M., Harris S. A. & Maxwell A. Small DNA circles as probes of DNA topology. Biochem Soc. Trans. (2013) 41, 565-570.

    Fogg J. M., Randell G. L., Pettitt B. M., Sumners D. L., Harris S. A. & Zechiedrich L. Bullied no more: When and how DNA shoves proteins around Quart. Rev. Biophys. (2012) 45, 257-299.

Sarah Harris

School of Physics and Astronomy
University of Leeds
Leeds, UK