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A stretched conformation of DNA with a biological role?

  • Niklas Bosaeus (a1), Anna Reymer (a2), Tamás Beke-Somfai (a3), Tom Brown (a4), Masayuki Takahashi (a5), Pernilla Wittung-Stafshede (a1), Sandra Rocha (a1) and Bengt Nordén (a6)...

Abstract

We have discovered a well-defined extended conformation of double-stranded DNA, which we call Σ-DNA, using laser-tweezers force-spectroscopy experiments. At a transition force corresponding to free energy change ΔG = 1·57 ± 0·12 kcal (mol base pair)−1 60 or 122 base-pair long synthetic GC-rich sequences, when pulled by the 3′−3′ strands, undergo a sharp transition to the 1·52 ± 0·04 times longer Σ-DNA. Intriguingly, the same degree of extension is also found in DNA complexes with recombinase proteins, such as bacterial RecA and eukaryotic Rad51. Despite vital importance to all biological organisms for survival, genome maintenance and evolution, the recombination reaction is not yet understood at atomic level. We here propose that the structural distortion represented by Σ-DNA, which is thus physically inherent to the nucleic acid, is related to how recombination proteins mediate recognition of sequence homology and execute strand exchange. Our hypothesis is that a homogeneously stretched DNA undergoes a ‘disproportionation’ into an inhomogeneous Σ-form consisting of triplets of locally B-like perpendicularly stacked bases. This structure may ensure improved fidelity of base-pair recognition and promote rejection in case of mismatch during homologous recombination reaction. Because a triplet is the length of a gene codon, we speculate that the structural physics of nucleic acids may have biased the evolution of recombinase proteins to exploit triplet base stacks and also the genetic code.

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Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

*Author for correspondence: B. Nordén, Chemistry and Chemical Engineering, Chalmers University of Technology. Email: norden@chalmers.se

References

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Arnott, S., Chandrasekaran, R., Millane, R. P. & Park, H. S. (1986). DNA-RNA hybrid secondary structures. Journal of Molecular Biology 188, 631640.
Bosaeus, N., El-Sagheer, A. H., Brown, T., Smith, S. B., Akerman, B., Bustamante, C. & Norden, B. (2012). Tension induces a base-paired overstretched DNA conformation. Proceedings of the National Academy of Sciences of the United States of America 109, 1517915184.
Bosaeus, N., El-Sagheer, A. H., Brown, T., Åkerman, B. & Nordén, B. (2014). Force-induced melting of DNA – Evidence for peeling and internal melting from force spectra on short synthetic duplex sequences. Nucleic Acids Research 42, 80838091.
Brown, B. A., Lowenhaupt, K., Wilbert, C. M., Hanlon, E. B. & Rich, A. (2000). The zalpha domain of the editing enzyme dsRNA adenosine deaminase binds left-handed Z-RNA as well as Z-DNA. Proceedings of the National Academy of Sciences of the United States of America 97, 1353213536.
Chen, Z., Yang, H. & Pavletich, N. P. (2008). Mechanism of homologous recombination from the RecA-ssDNA/dsDNA structures. Nature 453, 489494.
Cluzel, P., Lebrun, A., Heller, C., Lavery, R., Viovy, J.-L., Chatenay, D. & Caron, F. (1996). DNA: an extensible molecule. Science 271, 792794.
Crick, F. H. H. (1966). Codon–anticodon pairing: the wobble hypothesis. Journal of Molecular Biology 19, 548555.
Da̧bkowska, I., Gonzalez, H. V., Jurečka, P. & Hobza, P. (2005). Stabilization energies of the hydrogen-bonded and stacked structures of nucleic acid base pairs in the crystal geometries of CG, AT, and AC DNA steps and in the NMR geometry of the 5′-d(GCGAAGC)-3′ hairpin: complete basis set calculations at the MP2 and. Journal of Physical Chemistry A 109, 11311136.
Danilowicz, C., Limouse, C., Hatch, K., Conover, A., Coljee, V. W., Kleckner, N. & Prentiss, M. (2009). The structure of DNA overstretched from the 5′5′ ends differs from the structure of DNA overstretched from the 3′3′ ends. Proceedings of the National Academy of Sciences of the United States of America 106, 1319613201.
Deechongkit, S., Nguyen, H., Powers, E. T., Dawson, P. E., Gruebele, M. & Kelly, J. W. (2004). Context-dependent contributions of backbone hydrogen bonding to beta-sheet folding energetics. Nature 430, 101105.
De Vlaminck, I., van Loenhout, M. T. J. T. J., Zweifel, L., den Blanken, J., Hooning, K., Hage, S., Kerssemakers, J. & Dekker, C. (2012). Mechanism of homology recognition in DNA recombination from dual-molecule experiments. Molecular Cell 46, 616624.
Distasio, R. A., von Lilienfeld, O. A. & Tkatchenko, A. (2012). Collective many-body van der Waals interactions in molecular systems. Proceedings of the National Academy of Sciences of the United States of America 109, 1479114795.
Flory, J., Tsang, S. S. & Muniyappa, K. (1984). Isolation and visualization of active presynaptic filaments of recA protein and single-stranded DNA. Proceedings of the National Academy of Sciences of the United States of America 81, 70267030.
Fornander, L. H. H., Renodon-Corniére, A., Kuwabara, N., Ito, K., Tsutsui, Y., Shimizu, T., Iwasaki, H., Nordén, B., Takahashi, M. (2014). Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through organization of DNA bases in the presynaptic filament. Nucleic Acids Research 42, 23582365.
Friedman, R. A. & Honig, B. (1995). A free energy analysis of nucleic acid base stacking in aqueous solution. Biophysical Journal 69, 15281535.
Giudice, E., Várnai, P. & Lavery, R. (2003). Base pair opening within B-DNA: free energy pathways for GC and AT pairs from umbrella sampling simulations. Nucleic Acids Research 31, 14341443.
Guckian, K. M., Krugh, T. R. & Kool, E. T. (2000). Solution structure of a nonpolar, non-hydrogen-bonded base pair surrogate in DNA. Journal of the American Chemical Society 122, 68416847.
Hagmar, P., Norden, B., Baty, D., Chartier, M., Takahashi, M., Nordén, B., Baty, D., Chartier, M. & Takahashi, M. (1992). Structure of DNA-RecA complexes studied by residue differential linear dichroism and fluorescence spectroscopy for a genetically engineered RecA protein. Journal of Molecular Biology 226, 11931205.
Harris, S. A. A., Sands, Z. A. A. & Laughton, C. A. A. (2005). Molecular dynamics simulations of duplex stretching reveal the importance of entropy in determining the biomechanical properties of DNA. Biophysical Journal 88, 16841691.
Kabeláč, M., Zendlová, L., Řeha, D. & Hobza, P. (2005). Potential energy surfaces of an adenine−thymine base pair and its methylated analogue in the presence of one and two water molecules: molecular mechanics and correlated Ab initio study. Journal of Physical Chemistry B 109, 1220612213.
Kiianitsa, K. & Stasiak, A. (1997). Helical repeat of DNA in the region of homologous pairing. Proceedings of the National Academy of Sciences of the USA 94, 78377840.
Kool, E. T. T. (2001). Hydrogen bonding, base stacking, and steric effects in DNA replication. Annual Review of Biophysics and Biomolecular Structure 30, 122.
Koonin, E. V. V. & Novozhilov, A. S. S. (2009). Origin and evolution of the genetic code: the universal enigma. IUBMB Life 61, 99111.
Lagerkvist, U. (1978). ‘Two out of three’: an alternative method for codon reading. Proceedings of the National Academy of Sciences of the United States of America 75, 17591762.
Lu, X.-J. X. J., Shakked, Z. & Olson, W. K. W. K. (2000). A-form conformational motifs in ligand-bound DNA structures. Journal of Molecular Biology 300, 819840.
Mitchell, P. R. & Sigel, H. (1978). A proton nuclear-magnetic-resonance study of self-stacking in purine and pyrimidine nucleosides and nucleotides. European Journal of Biochemistry 88, 149154.
Morcillo, J., Gallego, E. & Peral, F. (1987). A critical study of the application of ultraviolet spectroscopy to the self-association of adenine, adenosine and 5′-AMP in aqueous solution. Journal of Molecular Structure 157, 353369.
Morimatsu, K., Takahashi, M. & Nordén, B. (2002). Arrangement of RecA protein in its active filament determined by polarized-light spectroscopy. Proceedings of the National Academy of Sciences of the United States of America 99, 1168811693.
Norden, B. (1977). General aspects on linear dichroism spectroscopy and its application. Spectroscopy Letters 10, 381400.
Nordén, B., Elvingson, C., Kubista, M., Sjöberg, B., Ryberg, H., Ryberg, M., Mortensen, K. & Takahashi, M. (1992). Structure of RecA-DNA complexes studied by combination of linear dichroism and small-angle neutron scattering measurements on flow-oriented samples. Journal of Molecular Biology 226, 11751191.
Nordén, B., Wittung-Stafshede, P., Ellouze, C., Kim, H.-K., Mortensen, K. & Takahashi, M. (1998). Base orientation of second DNA in RecA·DNA filaments: analysis by combination of linear dichroism and small angle neutron scattering in flow-oriented solution. Journal of Biological Chemistry 273, 1568215686.
Reymer, A., Frykholm, K., Morimatsu, K., Takahashi, M. & Nordén, B. (2009). Structure of human Rad51 protein filament from molecular modeling and site-specific linear dichroism spectroscopy. Proceedings of the National Academy of Sciences 106, 1324813253.
Řezáč, J. & Hobza, P. (2007). On the nature of DNA-duplex stability. Chemistry – A European Journal 13, 29832989.
Řezáč, J., Hobza, P. & Harris, S. A. (2010). Stretched DNA investigated using molecular-dynamics and quantum-mechanical calculations. Biophysical Journal 98, 101110.
Rich, A., Nordheim, A. & Wang, A. (1984). The chemistry and biology of left-handed Z-DNA. Annual Review of Biochemistry 53, 791846.
Ristic, D., Kanaar, R. & Wyman, C. (2011). Visualizing RAD51-mediated joint molecules: implications for recombination mechanism and the effect of sequence heterology. Nucleic Acids Research 39, 155167.
Saladin, A., Amourda, C., Poulain, P., Férey, N., Baaden, M., Zacharias, M., Delalande, O., Prévost, C., Nicolas, F. & Pr, C. (2010). Modeling the early stage of DNA sequence recognition within RecA nucleoprotein filaments. Nucleic Acids Research 38, 63136323.
Selmer, M., Dunham, C. M. M., Murphy, F. V. V. th, Weixlbaumer, A., Petry, S., Kelley, A. C. C., Weir, J. R. R. & Ramakrishnan, V. (2006). Structure of the 70S ribosome complexed with mRNA and tRNA. Science 313, 19351942.
Stasiak, A. & Di Capua, E. (1982). The helicity of DNA in complexes with recA protein. Nature 299, 185186.
Stasiak, A., Di Capua, E. & Koller, T. (1981). Elongation of duplex DNA by recA protein. Journal of Molecular Biology 151, 557564.
Story, R. M. M., Weber, I. T. T. & Steitz, T. A. T. A. A. (1992). The structure of the E. coli recA protein monomer and polymer. Nature 355, 318325.
Sutthibutpong, T., Matek, C., Benham, C., Slade, G. G. G., Noy, A., Laughton, C., Doye, J. P. K., Louis, A. A. A., Harris, S. A. A., JP, K. D., Louis, A. A. A. & Harris, S. A. A. (2016). Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation. Nucleic Acids Research 44, 91219130.
Swart, M., van der Wijst, T., Fonseca Guerra, C. & Bickelhaupt, F. M. (2007). π-π stacking tackled with density functional theory. Journal of Molecular Modeling 13, 12451257.
Takahashi, M. & Nordén, B. (1994). The cofactor ATP in DNA-RecA complexes is not intercalated between DNA bases. Journal of Molecular Recognition 7, 221226.
Williams, M. C., Rouzina, I. & Bloomfield, V. A. (2002). Thermodynamics of DNA interactions from single molecule stretching experiments. Accounts of Chemical Research 35, 159166.
Williams, R. C. & Spengler, S. J. (1986). Fibers of RecA protein and complexes of RecA protein and single-stranded phi X174 DNA as visualized by negative-stain electron microscopy. Journal of Molecular Biology 187, 109118.
Xiao, J., Lee, A. M. M. & Singleton, S. F. F. (2006). Construction and evaluation of a kinetic scheme for RecA-mediated DNA strand exchange. Biopolymers 81, 473496.
Xu, J., Zhao, L., Xu, Y., Zhao, W., Sung, P. & Wang, H.-W. (2017). Cryo-EM structures of human RAD51 recombinase filaments during catalysis of DNA-strand exchange. Nature Structural & Molecular Biology 24, 4046.
Yarus, M., Chen, I. A., Yarus, M. & Harris, T. (2010). Life from an RNA world: the ancestor within. Nature 330, 758.
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