Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Nov 1;89(21):10336–10340. doi: 10.1073/pnas.89.21.10336

Quadruplex structure of d(G3T4G3) stabilized by K+ or Na+ is an asymmetric hairpin dimer.

P V Scaria 1, S J Shire 1, R H Shafer 1
PMCID: PMC50333  PMID: 1438219

Abstract

The ends of chromosomes contain repeats of guanine-rich sequences that can assume highly compact conformations and are presumed necessary for their biological role in chromosomal stabilization and association. We have investigated the conformational behavior of d(G3T4G3) as a function of the addition of either KCl or NaCl, in the concentration range of 50-200 mM, by using a spectrum of physical techniques and conclude that these salts induce a quadruplex species composed of two strands, each in a hairpin conformation. When salt is added, a large positive signal appears near 290 nm in the CD spectra. UV thermal denaturation curves show a single concentration-dependent transition and provide data for quantitating the thermodynamics of quadruplex formation. In electrophoresis experiments, the quadruplex structure migrates as a single species and more rapidly than the unstructured single strand. NMR spectra in the presence of KCl or NaCl indicate that the structure formed is asymmetric. Equilibrium ultracentrifugation studies confirm that these quadruplexes are composed of two strands of d(G3T4G3). Possible models for this structure are discussed.

Full text

PDF
10336

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blackburn E. H. Telomeres: structure and synthesis. J Biol Chem. 1990 Apr 15;265(11):5919–5921. [PubMed] [Google Scholar]
  2. Blackburn E. H. The molecular structure of centromeres and telomeres. Annu Rev Biochem. 1984;53:163–194. doi: 10.1146/annurev.bi.53.070184.001115. [DOI] [PubMed] [Google Scholar]
  3. Evans T., Schon E., Gora-Maslak G., Patterson J., Efstratiadis A. S1-hypersensitive sites in eukaryotic promoter regions. Nucleic Acids Res. 1984 Nov 12;12(21):8043–8058. doi: 10.1093/nar/12.21.8043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. GELLERT M., LIPSETT M. N., DAVIES D. R. Helix formation by guanylic acid. Proc Natl Acad Sci U S A. 1962 Dec 15;48:2013–2018. doi: 10.1073/pnas.48.12.2013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gralla J., Crothers D. M. Free energy of imperfect nucleic acid helices. 3. Small internal loops resulting from mismatches. J Mol Biol. 1973 Aug 5;78(2):301–319. doi: 10.1016/0022-2836(73)90118-6. [DOI] [PubMed] [Google Scholar]
  6. Hardin C. C., Henderson E., Watson T., Prosser J. K. Monovalent cation induced structural transitions in telomeric DNAs: G-DNA folding intermediates. Biochemistry. 1991 May 7;30(18):4460–4472. doi: 10.1021/bi00232a013. [DOI] [PubMed] [Google Scholar]
  7. Hastie N. D., Allshire R. C. Human telomeres: fusion and interstitial sites. Trends Genet. 1989 Oct;5(10):326–331. doi: 10.1016/0168-9525(89)90137-6. [DOI] [PubMed] [Google Scholar]
  8. Henderson E., Hardin C. C., Walk S. K., Tinoco I., Jr, Blackburn E. H. Telomeric DNA oligonucleotides form novel intramolecular structures containing guanine-guanine base pairs. Cell. 1987 Dec 24;51(6):899–908. doi: 10.1016/0092-8674(87)90577-0. [DOI] [PubMed] [Google Scholar]
  9. Jin R. Z., Breslauer K. J., Jones R. A., Gaffney B. L. Tetraplex formation of a guanine-containing nonameric DNA fragment. Science. 1990 Oct 26;250(4980):543–546. doi: 10.1126/science.2237404. [DOI] [PubMed] [Google Scholar]
  10. Kang C., Zhang X., Ratliff R., Moyzis R., Rich A. Crystal structure of four-stranded Oxytricha telomeric DNA. Nature. 1992 Mar 12;356(6365):126–131. doi: 10.1038/356126a0. [DOI] [PubMed] [Google Scholar]
  11. Kilpatrick M. W., Torri A., Kang D. S., Engler J. A., Wells R. D. Unusual DNA structures in the adenovirus genome. J Biol Chem. 1986 Aug 25;261(24):11350–11354. [PubMed] [Google Scholar]
  12. Lipanov A. A., Quintana J., Dickerson R. E. Disordered single crystal evidence for a quadruple helix formed by guanosine 5'-monophosphate. J Biomol Struct Dyn. 1990 Dec;8(3):483–489. doi: 10.1080/07391102.1990.10507824. [DOI] [PubMed] [Google Scholar]
  13. Panyutin I. G., Kovalsky O. I., Budowsky E. I., Dickerson R. E., Rikhirev M. E., Lipanov A. A. G-DNA: a twice-folded DNA structure adopted by single-stranded oligo(dG) and its implications for telomeres. Proc Natl Acad Sci U S A. 1990 Feb;87(3):867–870. doi: 10.1073/pnas.87.3.867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sen D., Gilbert W. A sodium-potassium switch in the formation of four-stranded G4-DNA. Nature. 1990 Mar 29;344(6265):410–414. doi: 10.1038/344410a0. [DOI] [PubMed] [Google Scholar]
  15. Sen D., Gilbert W. Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 1988 Jul 28;334(6180):364–366. doi: 10.1038/334364a0. [DOI] [PubMed] [Google Scholar]
  16. Smith F. W., Feigon J. Quadruplex structure of Oxytricha telomeric DNA oligonucleotides. Nature. 1992 Mar 12;356(6365):164–168. doi: 10.1038/356164a0. [DOI] [PubMed] [Google Scholar]
  17. Sundquist W. I., Klug A. Telomeric DNA dimerizes by formation of guanine tetrads between hairpin loops. Nature. 1989 Dec 14;342(6251):825–829. doi: 10.1038/342825a0. [DOI] [PubMed] [Google Scholar]
  18. Wang Y., Jin R., Gaffney B., Jones R. A., Breslauer K. J. Characterization by 1H NMR of glycosidic conformations in the tetramolecular complex formed by d(GGTTTTTGG). Nucleic Acids Res. 1991 Sep 11;19(17):4619–4622. doi: 10.1093/nar/19.17.4619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wang Y., de los Santos C., Gao X. O., Greene K., Live D., Patel D. J. Multinuclear nuclear magnetic resonance studies of Na cation-stabilized complex formed by d(G-G-T-T-T-T-C-G-G) in solution. Implications for G-tetrad structures. J Mol Biol. 1991 Dec 5;222(3):819–832. doi: 10.1016/0022-2836(91)90513-6. [DOI] [PubMed] [Google Scholar]
  20. Williamson J. R., Raghuraman M. K., Cech T. R. Monovalent cation-induced structure of telomeric DNA: the G-quartet model. Cell. 1989 Dec 1;59(5):871–880. doi: 10.1016/0092-8674(89)90610-7. [DOI] [PubMed] [Google Scholar]
  21. Zakian V. A. Structure and function of telomeres. Annu Rev Genet. 1989;23:579–604. doi: 10.1146/annurev.ge.23.120189.003051. [DOI] [PubMed] [Google Scholar]
  22. Zimmerman S. B., Cohen G. H., Davies D. R. X-ray fiber diffraction and model-building study of polyguanylic acid and polyinosinic acid. J Mol Biol. 1975 Feb 25;92(2):181–192. doi: 10.1016/0022-2836(75)90222-3. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES