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Formation and structural determinants of multi-stranded guanine-rich DNA complexes.

K Poon1, R B Macgregor

  • 1Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Ontario, Canada.

Biophysical Chemistry
|June 14, 2000
PubMed
Summary

Guanine-rich oligonucleotides form two distinct structures: tetraplexes and frayed wires. The number of contiguous guanines dictates which complex forms, influencing stability and guanine accessibility.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Nucleic Acid Chemistry

Background:

  • Guanine-rich sequences are known to form non-canonical DNA structures.
  • Oligonucleotides can self-assemble into various complex architectures.
  • Understanding these structures is crucial for fields like epigenetics and therapeutics.

Purpose of the Study:

  • To investigate the structural diversity of d(T15,Gn) oligonucleotides.
  • To elucidate the factors controlling the formation of distinct guanine-rich complexes.
  • To characterize the differences between tetraplex and frayed wire structures.

Main Methods:

  • Synthesis of oligonucleotides with varying lengths of contiguous guanine repeats (n=4-15).
  • Structural analysis of formed complexes, including strand stoichiometry.

Related Experiment Videos

  • Dimethyl sulfate (DMS) footprinting to assess guanine N7 accessibility.

    • Main Results:

    • Two distinct structures, four-stranded tetraplexes and frayed wires, were identified.
    • Oligonucleotides with fewer contiguous guanines (n=5-8) predominantly form tetraplexes.
    • Oligonucleotides with more contiguous guanines (n>8) primarily form frayed wires.
    • Frayed wires exhibit different strand stoichiometry and N7 guanine accessibility compared to tetraplexes.
    • The number and arrangement of guanines are key determinants of complex stability.

    Conclusions:

    • The number of contiguous guanine residues dictates the formation of either tetraplex or frayed wire structures.
    • These two guanine-rich assemblies are stabilized by distinct guanine-guanine interactions.
    • Complex formation likely proceeds via parallel pathways with potentially shared intermediates.