skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

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) makesmore » 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.« less

Authors:
; ; ; ; ; ORCiD logo; ; ; ORCiD logo; ;
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1557360
Grant/Contract Number:  
AC02-05CH11231
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:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English

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.
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. doi:10.1073/pnas.1909122116.
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. doi:10.1073/pnas.1909122116.
@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}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1073/pnas.1909122116

Save / Share:

Works referenced in this record:

Osmotic stress, crowding, preferential hydration, and binding: A comparison of perspectives
journal, April 2000

  • Parsegian, V. A.; Rand, R. P.; Rau, D. C.
  • Proceedings of the National Academy of Sciences, Vol. 97, Issue 8
  • DOI: 10.1073/pnas.97.8.3987

Temperature-dependent optical properties of a torsional oscillator model for dinucleoside phosphates
journal, March 1968


Selective Stabilization of Triplex DNA by Poly(ethylene glycols)
journal, December 1995

  • Spink, C. H.; Chaires, J. B.
  • Journal of the American Chemical Society, Vol. 117, Issue 51
  • DOI: 10.1021/ja00156a038

Cryo-EM structures of human RAD51 recombinase filaments during catalysis of DNA-strand exchange
journal, December 2016

  • Xu, Jingfei; Zhao, Lingyun; Xu, Yuanyuan
  • Nature Structural & Molecular Biology, Vol. 24, Issue 1
  • DOI: 10.1038/nsmb.3336

Linear dichroism spectroscopy of nucleic acids
journal, February 1992

  • Norden, Bengt; Kubista, Mikael; Kurucsev, Tomas
  • Quarterly Reviews of Biophysics, Vol. 25, Issue 1
  • DOI: 10.1017/S0033583500004728

Base-stacking and base-pairing contributions into thermal stability of the DNA double helix
journal, January 2006


Model of RecA-Mediated Homologous Recognition
journal, December 2004


Macromolecular crowding induced elongation and compaction of single DNA molecules confined in a nanochannel
journal, September 2009

  • Zhang, C.; Shao, P. G.; van Kan, J. A.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 39
  • DOI: 10.1073/pnas.0904741106

DNA Polymorphism as an Origin of Adenine-Thymine Tract Length-Dependent Threading Intercalation Rate
journal, November 2008

  • Nordell, Pär; Westerlund, Fredrik; Reymer, Anna
  • Journal of the American Chemical Society, Vol. 130, Issue 44
  • DOI: 10.1021/ja804427q

The Effect of Molecular Crowding with Nucleotide Length and Cosolute Structure on DNA Duplex Stability
journal, November 2004

  • Nakano, Shu-ichi; Karimata, Hisae; Ohmichi, Tatsuo
  • Journal of the American Chemical Society, Vol. 126, Issue 44
  • DOI: 10.1021/ja0463029

Hydration of Watson−Crick Base Pairs and Dehydration of Hoogsteen Base Pairs Inducing Structural Polymorphism under Molecular Crowding Conditions
journal, March 2009

  • Miyoshi, Daisuke; Nakamura, Kaori; Tateishi-Karimata, Hisae
  • Journal of the American Chemical Society, Vol. 131, Issue 10
  • DOI: 10.1021/ja805972a

μABC: a systematic microsecond molecular dynamics study of tetranucleotide sequence effects in B-DNA
journal, September 2014

  • Pasi, Marco; Maddocks, John H.; Beveridge, David
  • Nucleic Acids Research, Vol. 42, Issue 19
  • DOI: 10.1093/nar/gku855

DNA manipulation, sorting, and mapping in nanofluidic systems
journal, January 2010

  • Levy, Stephen L.; Craighead, Harold G.
  • Chemical Society Reviews, Vol. 39, Issue 3
  • DOI: 10.1039/b820266b

DNA in nanochannels—directly visualizing genomic information
journal, January 2010

  • Persson, Fredrik; Tegenfeldt, Jonas O.
  • Chemical Society Reviews, Vol. 39, Issue 3
  • DOI: 10.1039/b912918a

Hydrogen Bonding, Base Stacking, and Steric Effects in DNA Replication
journal, June 2001


Strong DNA deformation required for extremely slow DNA threading intercalation by a binuclear ruthenium complex
journal, September 2014

  • Almaqwashi, Ali A.; Paramanathan, Thayaparan; Lincoln, Per
  • Nucleic Acids Research, Vol. 42, Issue 18
  • DOI: 10.1093/nar/gku859

Tension induces a base-paired overstretched DNA conformation
journal, September 2012

  • Bosaeus, N.; El-Sagheer, A. H.; Brown, T.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 38
  • DOI: 10.1073/pnas.1213172109

Properties of P-form DNA as revealed by circular dichroism
journal, August 1981


How the double helix breathes
journal, July 1987


Interaction between particles suspended in solutions of macromolecules
journal, December 1958


DNA Thermal Stability Depends on Solvent Viscosity
journal, April 2019

  • Stellwagen, Nancy C.; Stellwagen, Earle
  • The Journal of Physical Chemistry B, Vol. 123, Issue 17
  • DOI: 10.1021/acs.jpcb.9b01217

Expanded-Size Bases in Naturally Sized DNA:  Evaluation of Steric Effects in Watson−Crick Pairing
journal, September 2004

  • Gao, Jianmin; Liu, Haibo; Kool, Eric T.
  • Journal of the American Chemical Society, Vol. 126, Issue 38
  • DOI: 10.1021/ja048499a

A Hydrogen Exchange Method Using Tritium and Sephadex: Its Application to Ribonuclease *
journal, July 1963


Unraveling Base Stacking Driving Forces in DNA
journal, April 2016


The structural impact of DNA mismatches
journal, March 2015

  • Rossetti, Giulia; Dans, Pablo D.; Gomez-Pinto, Irene
  • Nucleic Acids Research, Vol. 43, Issue 8
  • DOI: 10.1093/nar/gkv254

Structure of strand-separted DNA in different environments studied by linear dichroism: LINEAR DICHROISM OF DNA
journal, September 1979


A stretched conformation of DNA with a biological role?
journal, January 2017


Molecular Recognition in Monolayers. Complementary Base Pairing in Dioleoylphosphatidyl Derivatives of Adenosine, Uridine, and Cytidine
journal, June 1997

  • Berti, Debora; Franchi, Lucia; Baglioni, Piero
  • Langmuir, Vol. 13, Issue 13
  • DOI: 10.1021/la970334a

Flexibility of DNA
journal, January 1974


Renaturation of DNA in ethanol-methanol solvent induced by complexation with methyl green: COMMUNICATIONS TO THE EDITOR
journal, February 1978


Double-stranded DNA in methanol-ethanol-buffer solvent system
journal, November 1976


Structure of human Rad51 protein filament from molecular modeling and site-specific linear dichroism spectroscopy
journal, July 2009

  • Reymer, A.; Frykholm, K.; Morimatsu, K.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 32
  • DOI: 10.1073/pnas.0902723106

Mechanism of homologous recombination from the RecA–ssDNA/dsDNA structures
journal, May 2008

  • Chen, Zhucheng; Yang, Haijuan; Pavletich, Nikola P.
  • Nature, Vol. 453, Issue 7194
  • DOI: 10.1038/nature06971

Linear dichroism studies of nucleic acids. II. Calculation of reduced dichroism curves of A-and B-form DNA
journal, December 1982


DNA-Binding of Semirigid Binuclear Ruthenium Complex Δ,Δ-[μ-(11,11‘-bidppz)(phen) 4 Ru 2 ] 4+ :  Extremely Slow Intercalation Kinetics
journal, October 2002

  • Wilhelmsson, L. Marcus; Westerlund, Fredrik; Lincoln, Per
  • Journal of the American Chemical Society, Vol. 124, Issue 41
  • DOI: 10.1021/ja027252f

Solvent effects on dinucleotide conformation
journal, March 1972


The B- to A-DNA Transition and the Reorganization of Solvent at the DNA Surface
journal, May 2005


Molecular Configuration in Sodium Thymonucleate
journal, April 1953

  • Franklin, Rosalind E.; Gosling, R. G.
  • Nature, Vol. 171, Issue 4356
  • DOI: 10.1038/171740a0

Double-Stranded DNA Dissociates into Single Strands When Dragged into a Poor Solvent
journal, November 2007

  • Cui, Shuxun; Yu, Jin; Kühner, Ferdinand
  • Journal of the American Chemical Society, Vol. 129, Issue 47
  • DOI: 10.1021/ja074776c

Evidence for hydrophobic catalysis of DNA strand exchange
journal, January 2015

  • Feng, B.; Westerlund, F.; Nordén, B.
  • Chemical Communications, Vol. 51, Issue 34
  • DOI: 10.1039/C5CC01515D

Nonaqueous solutions of DNA: Factors determining the stability of the helical configuration in solution
journal, June 1962


Biophysics of the DNA molecule
journal, September 1997


Sequence-dependent response of DNA to torsional stress: a potential biological regulation mechanism
journal, December 2017

  • Reymer, Anna; Zakrzewska, Krystyna; Lavery, Richard
  • Nucleic Acids Research, Vol. 46, Issue 4
  • DOI: 10.1093/nar/gkx1270

Hydrogen Exchange Studies of dna Structure
journal, February 1965

  • Printz, M. P.; Hippel, P. H. v.
  • Proceedings of the National Academy of Sciences, Vol. 53, Issue 2
  • DOI: 10.1073/pnas.53.2.363

Decreased Resistance to Bacterial Infection and Granulocyte Defects in IAP-Deficient Mice
journal, November 1996


Single-molecule FRET and linear dichroism studies of DNA breathing and helicase binding at replication fork junctions
journal, September 2013

  • Phelps, C.; Lee, W.; Jose, D.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 43
  • DOI: 10.1073/pnas.1314862110

Single-Chain Properties of Polyelectrolytes in Poor Solvent
journal, August 2003

  • Limbach, Hans Jörg; Holm, Christian
  • The Journal of Physical Chemistry B, Vol. 107, Issue 32
  • DOI: 10.1021/jp027606p

Circular dichroism and conformational polymorphism of DNA
journal, January 2009

  • Kypr, J.; Kejnovska, I.; Renciuk, D.
  • Nucleic Acids Research, Vol. 37, Issue 6
  • DOI: 10.1093/nar/gkp026

Hydrophobic Stacking of Bases and the Solvent Denaturation of dna
journal, December 1964


DNA strand exchange catalyzed by molecular crowding in PEG solutions
journal, January 2009

  • Feng, Bobo; Frykholm, Karolin; Nordén, Bengt
  • Chemical Communications, Vol. 46, Issue 43
  • DOI: 10.1039/c0cc03117h

Stabilization of DNA Structures with Poly(ethylene sodium phosphate)
journal, July 2015

  • Moriyama, Rui; Iwasaki, Yasuhiko; Miyoshi, Daisuke
  • The Journal of Physical Chemistry B, Vol. 119, Issue 36
  • DOI: 10.1021/acs.jpcb.5b03787

Unwinding of double-stranded DNA helix by dehydration.
journal, May 1981

  • Lee, C. H.; Mizusawa, H.; Kakefuda, T.
  • Proceedings of the National Academy of Sciences, Vol. 78, Issue 5
  • DOI: 10.1073/pnas.78.5.2838

The flow linear dichroism of DNA: Comparison with the bead-spring theory
journal, May 1978


Structure/function relationships in RecA protein-mediated homology recognition and strand exchange
journal, October 2015

  • Prentiss, Mara; Prévost, Chantal; Danilowicz, Claudia
  • Critical Reviews in Biochemistry and Molecular Biology, Vol. 50, Issue 6
  • DOI: 10.3109/10409238.2015.1092943

Monitoring the DNA Binding Kinetics of a Binuclear Ruthenium Complex by Energy Transfer:  Evidence for Slow Shuffling
journal, November 2005

  • Westerlund, Fredrik; Wilhelmsson, L. Marcus; Nordén, Bengt
  • The Journal of Physical Chemistry B, Vol. 109, Issue 44
  • DOI: 10.1021/jp0534838

Solvent-Induced DNA Conformational Transition
journal, February 2008