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Title: Hydrophobic catalysis and a potential biological role of DNA unstacking induced by environment effects

Abstract

Hydrophobic base stacking is a major contributor to DNA double-helix stability. We report the discovery of specific unstacking effects in certain semihydrophobic environments. Water-miscible ethylene glycol ethers are found to modify structure, dynamics, and reactivity of DNA by mechanisms possibly related to a biologically relevant hydrophobic catalysis. Spectroscopic data and optical tweezers experiments show that base-stacking energies are reduced while base-pair hydrogen bonds are strengthened. We propose that a modulated chemical potential of water can promote “longitudinal breathing” and the formation of unstacked holes while base unpairing is suppressed. Flow linear dichroism in 20% diglyme indicates a 20 to 30% decrease in persistence length of DNA, supported by an increased flexibility in single-molecule nanochannel experiments in poly(ethylene glycol). A limited (3 to 6%) hyperchromicity but unaffected circular dichroism is consistent with transient unstacking events while maintaining an overall average B-DNA conformation. Further information about unstacking dynamics is obtained from the binding kinetics of large thread-intercalating ruthenium complexes, indicating that the hydrophobic effect provides a 10 to 100 times increased DNA unstacking frequency and an “open hole” population on the order of 10–2 compared to 10–4 in normal aqueous solution. Spontaneous DNA strand exchange catalyzed by poly(ethylene glycol) makes us proposemore » that hydrophobic residues in the L2 loop of recombination enzymes RecA and Rad51 may assist gene recombination via modulation of water activity near the DNA helix by hydrophobic interactions, in the manner described here. We speculate that such hydrophobic interactions may have catalytic roles also in other biological contexts, such as in polymerases.« less

Authors:
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Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); Swedish Research Council (VR); Olle Engqvist Foundation; National Institutes of Health (NIH)
OSTI Identifier:
1557360
Alternate Identifier(s):
OSTI ID: 1625046
Grant/Contract Number:  
AC02-05CH11231; 2015-04020; 2015–5062; 2016/84; R01-HG006851; R01GM032543
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 116 Journal Issue: 35; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; science & technology - other topics; DNA; hydrophobic catalysis; threading intercalation; DNA polymerase; RecA

Citation Formats

Feng, Bobo, Sosa, Robert P., Mårtensson, Anna K. F., Jiang, Kai, Tong, Alex, Dorfman, Kevin D., Takahashi, Masayuki, Lincoln, Per, Bustamante, Carlos J., Westerlund, Fredrik, and Nordén, Bengt. Hydrophobic catalysis and a potential biological role of DNA unstacking induced by environment effects. United States: N. p., 2019. Web. doi:10.1073/pnas.1909122116.
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Feng, Bobo, Sosa, Robert P., Mårtensson, Anna K. F., Jiang, Kai, Tong, Alex, Dorfman, Kevin D., Takahashi, Masayuki, Lincoln, Per, Bustamante, Carlos J., Westerlund, Fredrik, & Nordén, Bengt. Hydrophobic catalysis and a potential biological role of DNA unstacking induced by environment effects. United States. https://doi.org/10.1073/pnas.1909122116
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Feng, Bobo, Sosa, Robert P., Mårtensson, Anna K. F., Jiang, Kai, Tong, Alex, Dorfman, Kevin D., Takahashi, Masayuki, Lincoln, Per, Bustamante, Carlos J., Westerlund, Fredrik, and Nordén, Bengt. Wed . "Hydrophobic catalysis and a potential biological role of DNA unstacking induced by environment effects". United States. https://doi.org/10.1073/pnas.1909122116.
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@article{osti_1557360,
title = {Hydrophobic catalysis and a potential biological role of DNA unstacking induced by environment effects},
author = {Feng, Bobo and Sosa, Robert P. and Mårtensson, Anna K. F. and Jiang, Kai and Tong, Alex and Dorfman, Kevin D. and Takahashi, Masayuki and Lincoln, Per and Bustamante, Carlos J. and Westerlund, Fredrik and Nordén, Bengt},
abstractNote = {Hydrophobic base stacking is a major contributor to DNA double-helix stability. We report the discovery of specific unstacking effects in certain semihydrophobic environments. Water-miscible ethylene glycol ethers are found to modify structure, dynamics, and reactivity of DNA by mechanisms possibly related to a biologically relevant hydrophobic catalysis. Spectroscopic data and optical tweezers experiments show that base-stacking energies are reduced while base-pair hydrogen bonds are strengthened. We propose that a modulated chemical potential of water can promote “longitudinal breathing” and the formation of unstacked holes while base unpairing is suppressed. Flow linear dichroism in 20% diglyme indicates a 20 to 30% decrease in persistence length of DNA, supported by an increased flexibility in single-molecule nanochannel experiments in poly(ethylene glycol). A limited (3 to 6%) hyperchromicity but unaffected circular dichroism is consistent with transient unstacking events while maintaining an overall average B-DNA conformation. Further information about unstacking dynamics is obtained from the binding kinetics of large thread-intercalating ruthenium complexes, indicating that the hydrophobic effect provides a 10 to 100 times increased DNA unstacking frequency and an “open hole” population on the order of 10–2 compared to 10–4 in normal aqueous solution. Spontaneous DNA strand exchange catalyzed by poly(ethylene glycol) makes us propose that hydrophobic residues in the L2 loop of recombination enzymes RecA and Rad51 may assist gene recombination via modulation of water activity near the DNA helix by hydrophobic interactions, in the manner described here. We speculate that such hydrophobic interactions may have catalytic roles also in other biological contexts, such as in polymerases.},
doi = {10.1073/pnas.1909122116},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 35,
volume = 116,
place = {United States},
year = {2019},
month = {8}
}
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https://doi.org/10.1073/pnas.1909122116
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Figures / Tables:

Fig. 1 Fig. 1: Flow LD confirms B-DNA and indicates shorter persistence length in diglyme. (A) DNA LD spectra (720 rpm; see SI Appendix, Figs. S14–S16 for all speeds) with wavelength-independent LDr is consistent with bases near perpendicular to helix axis in diglyme and glycerol. (B) LDr in diglyme is less negativemore » than in glycerol of the same viscosity. Hence, DNA persistence length is shortened in diglyme. Extrapolation to zero flow gradient indicates persistence length in diglyme between 70 and 81% of that in glycerol (see text and SI Appendix, section 1d).« less
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