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Disorder and Strain-Induced Complexity in Functional Materials pp 273–292Cite as

Entropy–Driven Conformations Controlling DNA Functions

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Part of the book series: Springer Series in Materials Science ((SSMATERIALS,volume 148))

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.

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Acknowledgments

We gratefully acknowledge all our collaborators with whom we have coauthored the original works summarized here. This work was carried out under the auspices of the National Nuclear Security Administration of the US Department of Energy at Los Alamos National Laboratory under Contract No. DE-AC52–06NA25396.

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Authors and Affiliations

  1. Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA

    A. R. Bishop, K. Ø. Rasmussen & Boian S. Alexandrov

  2. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    A. Usheva

Authors
  1. A. R. Bishop
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  2. K. Ø. Rasmussen
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  3. A. Usheva
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  4. Boian S. Alexandrov
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Corresponding author

Correspondence to A. R. Bishop .

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Editors and Affiliations

  1. , Graduate School of Engineering, Osaka University, Yamada-oka, Suita 2-1, Osaka, 565-0871, Japan

    Tomoyuki Kakeshita

  2. , Graduate School of Engineering, Osaka University, Yamada-oka, Suita 2-1, Osaka, 565-0871, Japan

    Takashi Fukuda

  3. Theoretical Division, T-11, MS B262, Los Alamos National Lab, Los Alamos, 87545, New Mexico, USA

    Avadh Saxena

  4. Dept. d'Estructura i Constituents, de la Matèria, Universidad de Barcelona, Diagonal 647, Barcelona, 08028, Spain

    Antoni Planes

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Bishop, A.R., Rasmussen, K.Ø., Usheva, A., Alexandrov, B.S. (2012). Entropy–Driven Conformations Controlling DNA Functions. In: Kakeshita, T., Fukuda, T., Saxena, A., Planes, A. (eds) Disorder and Strain-Induced Complexity in Functional Materials. Springer Series in Materials Science, vol 148. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-20943-7_14

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  • DOI: https://doi.org/10.1007/978-3-642-20943-7_14

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