"The DNA Structure Responds Differently to Physiological Concentrations of K⁺ or Na^+"

Brahim Heddi ¹, Nicolas Foloppe ^{1, @}, Edith Hantz ², and Brigitte Hartmann ^{1, @},

¹ Laboratoire de Biochimie Théorique, CNRS UPR 9080, Institut de Biologie Physico-chimique, 13 rue Pierre et Marie Curie, Paris 75005, France
² BioMoCeTi, Université Paris 13, 74 rue Marcel Cachin, Bobigny 93017, France

E-mail:  briggite@ibpc.fr     or:    nf_research@hotmail.com

The influence of monovalent cations on DNA conformation and readout is an open question. This NMR study of DNA with either Na⁺ or K⁺ at physiological concentrations shows that the nature of the cation affects the ³¹P chemical shifts (oP) and the sequential distances H2'_i–H6/8_i+1, H2_''i–H6/8_i+1, and H6/8_i–H6/8_i+1. The oP and distance variations ascertain that the nature of the cation affects the DNA overall structure, i.e. both the conformational equilibria between the backbone BI (e–d < 0°) and BII (e–d > 0°) states and the helical parameters, via their strong mechanical coupling. These results reveal that Na⁺ and K⁺ interactions with DNA are different and sequence-dependent. These ions modulate the overall intrinsic properties of DNA, and possibly its packaging and readout.

Keywords: DNA structure; BI–BII equilibrium; counterion effects; sequence effects; ³¹P NMR

Abbreviations: MD, molecular dynamics; HSQC, heteronuclear single quantum coherence.

Introduction
Results
Concluding Discussion
Materials and Methods
Sample preparation
NMR spectroscopy
Crystallographic data
Acknowledgements
References
Thumbnail images

Fig. 1. Illustration of the BI (left) and BII (right) phosphate linkage conformations with a CpA dinucleotide. The lines depict the sequential distances between H8 (red) of the adenine and H2_i/H2_'' (green) or H6 (red) of the cytosine.

Fig: 2. One-dimensional ³¹P NMR spectra of the JunFos oligomer in Na⁺ (left) and K⁺ (right) buffers at 27 °C. The peaks corresponding to the phosphate of G23pA24, very sensitive to the type of counterion, are indicated by an arrow.

Recent NMR studies by Brahim Heddi, Nicolas Foloppe, Edith Hantz, and Brigitte Hartmann reveal that
DNA in solution assumes different structures within either K⁺ or Na⁺ at physiological concentrations, and correlates with earlier observations that active DNA within intact nuclei requires a Na⁺ environment.

1. Heddi B, Foloppe N, Oguey C, and Hartmann B, "Importance of Accurate DNA Structures in Solution: The Jun–Fos Model", J. Molec. Biol. vol. 382, issue 4, 17 October 2008, Pages 956-970.

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3. Frenster JH, Allfrey VG, and Mirsky AE, "Metabolism and Morphology of Ribonucleoprotein Particles from the Cell Nucleus of Lymphocytes", Proc. Natl. Acad. Sci. U.S. vol. 46, pp. 432-444 (April, 1960).

4. Frenster JH, Allfrey VG, and Mirsky AE, "In-Vitro Incorporation of Amino Acids into the Proteins of Isolated Nuclear Ribosomes", Biochim. Biophys. Acta vol. 47: pp. 130-47 (1961).

5. Crick F, "Central Dogma of Molecular Biology", Nature vol. 227: pp. 561-563 (August 8, 1970).

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