Abstract
The remarkable conformational lability of poly(dG-m5dC):poly(dG-m5dC) is demonstrated by the observation of an acid-mediated conformational hysteresis. An acid-mediated Z conformation that exists in solutions containing low sodium concentrations that would normally favor the B conformation is described in this report. This Z conformation is reached by an acid-base titration of a B-poly(dG-m5dC):poly(dG-m5dC) solution which is not far from the B-Z transition midpoint. The resulting Z conformation is thermally very stable, with direct melting into single strands at approximately 100 degrees C. In contrast, the B form DNA, initially in solutions of the same ionic strength but without exposure to acidic pH, exhibits a biphasic melting profile, with conversion into the Z form (with high cooperativity) prior to an eventual denaturation into single strands at around 100 degrees C. Cooling experiments reveal that such biphasic transitions are quite reversible. The transition midpoint for the thermally poised B to Z transformation depends strongly on the NaCl concentration and varies with sample batch. The acid-mediated Z form binds ethidium more weakly than its B counterpart, and the ethidium induced Z to B conversion occurs in a step-wise (non-allosteric) fashion without the requirement of a threshold concentration. The acid-mediated as well as the thermally poised Z conformations are reversed by the addition of EDTA, suggesting the involvement of trace amounts of multivalent metal ions.
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Selected References
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- Behe M. J., Felsenfeld G., Szu S. C., Charney E. Temperature-dependent conformational transitions in poly(dG-dC) and poly(dG-m5dC). Biopolymers. 1985 Feb;24(2):289–300. doi: 10.1002/bip.360240202. [DOI] [PubMed] [Google Scholar]
- Behe M., Felsenfeld G. Effects of methylation on a synthetic polynucleotide: the B--Z transition in poly(dG-m5dC).poly(dG-m5dC). Proc Natl Acad Sci U S A. 1981 Mar;78(3):1619–1623. doi: 10.1073/pnas.78.3.1619. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen F. M. Base protonation facilitates B-Z interconversions of poly(dG-dC) X poly(dG-dC). Biochemistry. 1984 Dec 4;23(25):6159–6165. doi: 10.1021/bi00320a041. [DOI] [PubMed] [Google Scholar]
- Chen H. H., Behe M. J., Rau D. C. Critical amount of oligovalent ion binding required for the B-Z transition of poly (dG-m5dC). Nucleic Acids Res. 1984 Mar 12;12(5):2381–2389. doi: 10.1093/nar/12.5.2381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Doerfler W. DNA methylation and gene activity. Annu Rev Biochem. 1983;52:93–124. doi: 10.1146/annurev.bi.52.070183.000521. [DOI] [PubMed] [Google Scholar]
- Feuerstein B. G., Marton L. J., Keniry M. A., Wade D. L., Shafer R. H. New DNA polymorphism: evidence for a low salt, left-handed form of poly(dG-m5dC). Nucleic Acids Res. 1985 Jun 11;13(11):4133–4141. doi: 10.1093/nar/13.11.4133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krueger W. C., Prairie M. D. A low-salt form of poly(dG-5M-dC).poly(dG-5M-dC). Biopolymers. 1985 May;24(5):905–910. doi: 10.1002/bip.360240513. [DOI] [PubMed] [Google Scholar]
- Latha P. K., Brahmachari S. K. A novel structural transition in poly(dG-Me5dC):Z in equilibrium B in equilibrium Z. FEBS Lett. 1985 Mar 25;182(2):315–318. doi: 10.1016/0014-5793(85)80323-9. [DOI] [PubMed] [Google Scholar]
- Pohl F. M., Jovin T. M., Baehr W., Holbrook J. J. Ethidium bromide as a cooperative effector of a DNA structure. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3805–3809. doi: 10.1073/pnas.69.12.3805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pohl F. M., Jovin T. M. Salt-induced co-operative conformational change of a synthetic DNA: equilibrium and kinetic studies with poly (dG-dC). J Mol Biol. 1972 Jun 28;67(3):375–396. doi: 10.1016/0022-2836(72)90457-3. [DOI] [PubMed] [Google Scholar]
- Rich A., Nordheim A., Wang A. H. The chemistry and biology of left-handed Z-DNA. Annu Rev Biochem. 1984;53:791–846. doi: 10.1146/annurev.bi.53.070184.004043. [DOI] [PubMed] [Google Scholar]
- Robert-Nicoud M., Arndt-Jovin D. J., Zarling D. A., Jovin T. M. Immunological detection of left-handed Z DNA in isolated polytene chromosomes. Effects of ionic strength, pH, temperature and topological stress. EMBO J. 1984 Apr;3(4):721–731. doi: 10.1002/j.1460-2075.1984.tb01875.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roy K. B., Miles H. T. A thermally driven interconversion of B and Z-dna. Biochem Biophys Res Commun. 1983 Aug 30;115(1):100–105. doi: 10.1016/0006-291x(83)90974-9. [DOI] [PubMed] [Google Scholar]
- Spodheim M., Neumann E. Ionic strength dependence of the hysteresis in the polyriboadenylate-polyribouridylate system. Biophys Chem. 1975 Apr;3(2):109–124. doi: 10.1016/0301-4622(75)80001-9. [DOI] [PubMed] [Google Scholar]
- Thamann T. J., Lord R. C., Wang A. H., Rich A. The high salt form of poly(dG-dC).poly(dG-dC) is left-handed Z-DNA: Raman spectra of crystals and solutions. Nucleic Acids Res. 1981 Oct 24;9(20):5443–5457. doi: 10.1093/nar/9.20.5443. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thiele D., Marck C., Schneider C., Guschlbauer W. Protonated polynucleotides structures - 23. The acid-base hysteresis of poly(dG).poly(dC). Nucleic Acids Res. 1978 Jun;5(6):1997–2012. doi: 10.1093/nar/5.6.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas T. J., Bloomfield V. A. Toroidal condensation of Z DNA and identification of an intermediate in the B to Z transition of poly(dG-m5dC) X poly(dG-m5dC). Biochemistry. 1985 Jan 29;24(3):713–719. doi: 10.1021/bi00324a026. [DOI] [PubMed] [Google Scholar]
- Walker G. T., Stone M. P., Krugh T. R. Ethidium binding to left-handed (Z) DNAs results in regions of right-handed DNA at the intercalation site. Biochemistry. 1985 Dec 3;24(25):7462–7471. doi: 10.1021/bi00346a065. [DOI] [PubMed] [Google Scholar]
- Wang A. H., Quigley G. J., Kolpak F. J., Crawford J. L., van Boom J. H., van der Marel G., Rich A. Molecular structure of a left-handed double helical DNA fragment at atomic resolution. Nature. 1979 Dec 13;282(5740):680–686. doi: 10.1038/282680a0. [DOI] [PubMed] [Google Scholar]
- Woisard A., Fazakerley G. V., Guschlbauer W. Z-DNA is formed by poly (dC-dG) and poly (dm5C-dG) at micro or nanomolar concentrations of some zinc(II) and copper(II) complexes. J Biomol Struct Dyn. 1985 Jun;2(6):1205–1220. doi: 10.1080/07391102.1985.10507633. [DOI] [PubMed] [Google Scholar]
- van de Sande J. H., Jovin T. M. Z* DNA, the left-handed helical form of poly[d(G-C)] in MgCl2-ethanol, is biologically active. EMBO J. 1982;1(1):115–120. doi: 10.1002/j.1460-2075.1982.tb01133.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
