Entropy-driven conformations controlling DNA functions

Abstract

In memory of Jim Krumhansl we summarize our growing level of understanding of the origins and functional roles of specific nonlinear conformational excitations ("bubbles") in DNA. We present a number of results that point toward the conclusion that DNA is capable of directing major aspects of its own lifecycle, governed by the laws of equilibrium thermodynamics. First, we discuss a series of experimental and theoretical research results that demonstrate a correlation between DNA bubbles and essential biological processes such as DNA transcription and DNA-protein binding. Specifically, we discuss how, through a synergetic combination of modeling and experiments, we have developed an extended version of the Peyrard-Bishop-Dauxois model, and used it to predict specific properties, such as bubble location, size, and duration, of DNA breathing. Applying this framework, we show a number of examples that demonstrate that specific breathing properties lead to enhancements in transcription activity and DNA-protein binding efficiency. Second, we show that DNA may be able to apply its complex conformational dynamics to facilitate its own repair. We demonstrate this in the context of specific DNA damage that has been documented to arise from exposure to UV radiation. Finally, we discuss our ongoing attempts to harness our knowledge of DNA conformation and dynamics and their impact on function to help predict transcription initiation sites in entire genomes. We apply techniques from bioinformatics and statistical learning to incorporate the above features into a more predictive framework. © Springer-Verlag Berlin Heidelberg 2012.