The stability and number of nucleating interactions determine DNA hybridisation rates in the absence of secondary structure
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Published version
Author(s)
Type
Journal Article
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. 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 our observations. 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. Our results indicate that
greater repetition of Watson-Crick pairs increases the number of initial states able to proceed to full
hybridisation, with the stability of those pairings dictating the likelihood of such progression, thus providing
new insight into the physical factors underpinning DNA hybridisation rates.
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. 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 our observations. 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. Our results indicate that
greater repetition of Watson-Crick pairs increases the number of initial states able to proceed to full
hybridisation, with the stability of those pairings dictating the likelihood of such progression, thus providing
new insight into the physical factors underpinning DNA hybridisation rates.
Date Issued
2022-08-12
Date Acceptance
2022-06-25
Citation
Nucleic Acids Research, 2022, 50 (14), pp.7829-7841
ISSN
0305-1048
Publisher
Oxford University Press
Start Page
7829
End Page
7841
Journal / Book Title
Nucleic Acids Research
Volume
50
Issue
14
Copyright Statement
© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License
(http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work
is properly cited. For commercial re-use, please contact journals.permissions@oup.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License
(http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work
is properly cited. For commercial re-use, please contact journals.permissions@oup.com
License URL
Sponsor
The Royal Society
Identifier
https://academic.oup.com/nar/article/50/14/7829/6649941
Grant Number
UF150067
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
HELIX-COIL TRANSITION
SINGLE-STRANDED-DNA
NONENZYMATIC BASE RECOGNITION
SUPERRESOLUTION MICROSCOPY
MOLECULE KINETICS
NUCLEIC-ACIDS
FOLDING DNA
THERMODYNAMICS
PARAMETERS
COMPLEMENTARY
DNA
Kinetics
Nucleic Acid Conformation
Nucleic Acid Hybridization
Thermodynamics
DNA
Nucleic Acid Hybridization
Nucleic Acid Conformation
Kinetics
Thermodynamics
Developmental Biology
05 Environmental Sciences
06 Biological Sciences
08 Information and Computing Sciences
Publication Status
Published
Date Publish Online
2022-07-26