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. 1994 May 11;22(9):1600–1606. doi: 10.1093/nar/22.9.1600

Intramolecular folding of a fragment of the cytosine-rich strand of telomeric DNA into an i-motif.

J L Leroy 1, M Guéron 1, J L Mergny 1, C Hélène 1
PMCID: PMC308035  PMID: 8202359

Abstract

In the recently discovered i-motif, four stretches of cytosine form two parallel-stranded duplexes whose C.C+ base pairs are fully intercalated. The i-motif may be recognized by characteristic Overhauser cross-peaks of the proton NMR spectrum, reflecting short H1'-H1' distances across the minor groove, and short internucleotide amino-proton-H2'/H2" across the major groove. We report the observation of such cross-peaks in the spectra of a fragment of the C-rich telomeric strand of vertebrates, d[CCCTAA]3CCC. The spectra also demonstrate that the cytosines are base-paired and that proton exchange is very slow, as reported previously for the i-motif. From UV absorbance and gel chromatography measurements, we assign these properties to an i-motif which includes all or nearly all the cytosines, and which is formed by intramolecular folding at slightly acid or neutral pH. A fragment of telomeric DNA of Tetrahymena, d[CCCCAA]3CCCC, has the same properties. Hence four consecutive C stretches of a C-rich telomeric strand can fold into an i-motif. Hypothetically, this could occur in vivo.

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Selected References

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

  1. Ahmed S., Henderson E. Formation of novel hairpin structures by telomeric C-strand oligonucleotides. Nucleic Acids Res. 1992 Feb 11;20(3):507–511. doi: 10.1093/nar/20.3.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ahmed S., Kintanar A., Henderson E. Human telomeric C-strand tetraplexes. Nat Struct Biol. 1994 Feb;1(2):83–88. doi: 10.1038/nsb0294-83. [DOI] [PubMed] [Google Scholar]
  3. Alvarez L., Evans J. W., Wilks R., Lucas J. N., Brown J. M., Giaccia A. J. Chromosomal radiosensitivity at intrachromosomal telomeric sites. Genes Chromosomes Cancer. 1993 Sep;8(1):8–14. doi: 10.1002/gcc.2870080103. [DOI] [PubMed] [Google Scholar]
  4. Becker E. D., Miles H. T., Bradley R. B. Nuclear magnetic resonance studies of methyl derivatives of cytosine. J Am Chem Soc. 1965 Dec 20;87(24):5575–5582. doi: 10.1021/ja00952a011. [DOI] [PubMed] [Google Scholar]
  5. Cantor C. R., Warshaw M. M., Shapiro H. Oligonucleotide interactions. 3. Circular dichroism studies of the conformation of deoxyoligonucleotides. Biopolymers. 1970;9(9):1059–1077. doi: 10.1002/bip.1970.360090909. [DOI] [PubMed] [Google Scholar]
  6. Gehring K., Leroy J. L., Guéron M. A tetrameric DNA structure with protonated cytosine.cytosine base pairs. Nature. 1993 Jun 10;363(6429):561–565. doi: 10.1038/363561a0. [DOI] [PubMed] [Google Scholar]
  7. Gilson E., Laroche T., Gasser S. M. Telomeres and the functional architecture of the nucleus. Trends Cell Biol. 1993 Apr;3(4):128–134. doi: 10.1016/0962-8924(93)90175-z. [DOI] [PubMed] [Google Scholar]
  8. Gilson E., Roberge M., Giraldo R., Rhodes D., Gasser S. M. Distortion of the DNA double helix by RAP1 at silencers and multiple telomeric binding sites. J Mol Biol. 1993 May 20;231(2):293–310. doi: 10.1006/jmbi.1993.1283. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Leroy J. L., Gehring K., Kettani A., Guéron M. Acid multimers of oligodeoxycytidine strands: stoichiometry, base-pair characterization, and proton exchange properties. Biochemistry. 1993 Jun 15;32(23):6019–6031. doi: 10.1021/bi00074a013. [DOI] [PubMed] [Google Scholar]
  11. Manzini G., Xodo L. E., Gasparotto D., Quadrifoglio F., van der Marel G. A., van Boom J. H. Triple helix formation by oligopurine-oligopyrimidine DNA fragments. Electrophoretic and thermodynamic behavior. J Mol Biol. 1990 Jun 20;213(4):833–843. doi: 10.1016/S0022-2836(05)80267-0. [DOI] [PubMed] [Google Scholar]
  12. Rougée M., Faucon B., Mergny J. L., Barcelo F., Giovannangeli C., Garestier T., Hélène C. Kinetics and thermodynamics of triple-helix formation: effects of ionic strength and mismatches. Biochemistry. 1992 Sep 29;31(38):9269–9278. doi: 10.1021/bi00153a021. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Wang Y., Patel D. J. Solution structure of the human telomeric repeat d[AG3(T2AG3)3] G-tetraplex. Structure. 1993 Dec 15;1(4):263–282. doi: 10.1016/0969-2126(93)90015-9. [DOI] [PubMed] [Google Scholar]

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