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Mechanisms underlying sequence-dependent DNA hybridisation rates in the absence of secondary structure

Sophie Hertel, Richard E. Spinney, Stephanie Y. Xu, Thomas E. Ouldridge, Richard G. Morris, View ORCID ProfileLawrence K. Lee
doi: https://doi.org/10.1101/2021.12.17.473246
Sophie Hertel
1EMBL Australia Node for Single Molecule Science, School of Medical Sciences, UNSW Sydney, 2052, Australia
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Richard E. Spinney
1EMBL Australia Node for Single Molecule Science, School of Medical Sciences, UNSW Sydney, 2052, Australia
2School of Physics, University of New South Wales - Sydney 2052, Australia
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Stephanie Y. Xu
1EMBL Australia Node for Single Molecule Science, School of Medical Sciences, UNSW Sydney, 2052, Australia
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Thomas E. Ouldridge
3Department of Bioengineering and Centre for Synthetic Biology, Imperial College London, London, SW7 2AZ, United Kingdom
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Richard G. Morris
1EMBL Australia Node for Single Molecule Science, School of Medical Sciences, UNSW Sydney, 2052, Australia
2School of Physics, University of New South Wales - Sydney 2052, Australia
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Lawrence K. Lee
1EMBL Australia Node for Single Molecule Science, School of Medical Sciences, UNSW Sydney, 2052, Australia
4ARC Centre of Excellence in Synthetic Biology, University of New South Wales, Sydney, Australia
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  • ORCID record for Lawrence K. Lee
  • For correspondence: lawrence.lee@unsw.edu.au
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ABSTRACT

The kinetics of DNA hybridisation are fundamental to biological processes and DNA-based technologies. However, the precise physical mechanisms that determine why different DNA sequences hybridise at different rates are not well understood. Secondary structure is one predictable factor that influences hybridisation rates but is not sufficient on its own to fully explain the observed sequence-dependent variance. Consequently, to achieve a good correlation with experimental data, current prediction algorithms require many parameters that provide little mechanistic insight into DNA hybridisation. In this context, we measured hybridisation rates of 43 different DNA sequences that are not predicted to form secondary structure and present a parsimonious physically justified model to quantify their hybridisation rates. Accounting only for the combinatorics of complementary nucleating interactions and their sequence-dependent stability, the model achieves good correlation with experiment with only two free parameters, thus providing new insight into the physical factors underpinning DNA hybridisation rates.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/llee0905/DNA-bind

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted December 18, 2021.
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Mechanisms underlying sequence-dependent DNA hybridisation rates in the absence of secondary structure
Sophie Hertel, Richard E. Spinney, Stephanie Y. Xu, Thomas E. Ouldridge, Richard G. Morris, Lawrence K. Lee
bioRxiv 2021.12.17.473246; doi: https://doi.org/10.1101/2021.12.17.473246
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Mechanisms underlying sequence-dependent DNA hybridisation rates in the absence of secondary structure
Sophie Hertel, Richard E. Spinney, Stephanie Y. Xu, Thomas E. Ouldridge, Richard G. Morris, Lawrence K. Lee
bioRxiv 2021.12.17.473246; doi: https://doi.org/10.1101/2021.12.17.473246

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