Conformational aspects of an uncharged phosphate analogon built in at the branch-point of a DNA four-way junction

J Mol Biol. 1996 Sep 27;262(3):349-57. doi: 10.1006/jmbi.1996.0518.

Abstract

Electrostatic interactions appear to be important in the conformation and dynamics of DNA four-way junctions. Particularly, the Coulomb repulsion between two approaching phosphate groups at the site of strand exchange is commonly supposed to have a negative influence on the thermodynamic stability of the fully stacked conformation. We synthesized a unimolecular DNA four-way junction containing an uncharged methylene-acetal linkage, -O3'-CH2-O5'-, instead of a regular phosphodiester linkage, -O3'-PO2-O5'-, between two specific residues at the branch-point to examine the effect of charge removal. Complete sequential 1H-NMR assignments of the non-exchangeable base protons and H1'/H2'/H2" sugar protons were obtained with the aid of NOESY and TOCSY experiments. On the basis of the NMR data it is concluded that the stacking arrangement at the branch-point of the modified oligonucleotide is similar to that of the previously studied parent four-way junction. Surprisingly, this is not the stacking arrangement in which the close phosphate-phosphate contact at the site of strand exchange would be absent. Some implications of this novel information regarding the role of the phosphate-phosphate repulsion in four-way junctions are discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Nucleic Acid Conformation*
  • Oligonucleotides / chemistry
  • Phosphorus Isotopes
  • Protons
  • Tritium

Substances

  • Oligonucleotides
  • Phosphorus Isotopes
  • Protons
  • Tritium
  • DNA