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Quadruplex structure of Oxytricha telomeric DNA oligonucleotides

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Abstract

THE telomeres of most eukaryotes contain a repeating G-rich sequence with the consensus d(T/A)1–4G1–8, of which 12–16 bases form a 3' single-strand overhang beyond the telomeric duplex1. It has been proposed that these G-rich oligonucleotides associate to form four-stranded structures from one2–4, two2,5 or four6,7 individual strands and that these structures may be relevant in vivo. The proposed structures contain Hoogsteen base-paired G-quartets, precedent for which has been in the literature for many years8. Here we use 1H NMR spectroscopy to study the conformations of the DNA oligonucleotides d(G4T4G4) (Oxy-1.5) and d(G4T4G4T4G4T4G4) (Oxy-3.5) which contain the Oxytricha telomere repeat (T4G4). We find that these molecules fold to form a symmetrical bimolecular and an intramolecular quadruplex, respectively. Both structures have four G-quartets formed from nucleotides that are alternately syn and anti along each strand. This arrangement differs from earlier models in which the strands are alternately all syn or all anti2,3,5. The T4 loops in Oxy-1.5 are on opposite ends of the quadruplex and loop diagonally across the G-quartet, resulting in adjacent strands being alternately parallel and antiparallel.

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  1. Department of Chemistry and Biochemistry and Molecular Biology Institute, University of California, Los Angeles, California, 90024, USA

    Flint W. Smith & Juli Feigon

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  1. Flint W. Smith
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  2. Juli Feigon
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Smith, F., Feigon, J. Quadruplex structure of Oxytricha telomeric DNA oligonucleotides. Nature 356, 164–168 (1992). https://doi.org/10.1038/356164a0

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  • DOI: https://doi.org/10.1038/356164a0

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