DNA . RNA heteroduplex containing 8-oxo-7,8-dihydroguanosine: base pairing, structures, and thermodynamic stability

J Biochem Mol Biol. 2004 Nov 30;37(6):657-62. doi: 10.5483/bmbrep.2004.37.6.657.

Abstract

Oligoribonucleotides containing 8-oxo-7,8-dihydroguanosine (8-oxoG) and 8-oxo-7,8-dihydro-2'-O-methylguanosine (8-oxoG-Me) were synthesized. The base pairing properties of 8-oxoG and 8-oxoG-Me in oligoribonucleotide in cDNA synthesis by reverse transcriptases were studied. dCMP was preferentially incorporated into the site opposite 8-oxoG or 8-oxoG-Me than into other dNMPs. TMP and dCMP were inserted preferentially into sites opposite 8-oxoG or 8-oxoG by reverse transcriptases. HIV-RT did not incorporate TMP, but RAV2-RT incorporated 50% more TMP than dCMP into the site opposite 8-oxoG. In the site opposite 8-oxoG-Me TMP was substantially incorporated by HIV-RT or RAV2-RT. Thermodynamic analysis of the DNA.RNA heteroduplex containing 8-oxoG revealed that 8-oxoG and 8-oxoG-Me formed base pairs with cytidine and thymidine with similar stability. The thermodynamic parameter (DeltaG degrees ) demonstrated that the formation of duplexes between 8-oxoG or 8-oxoG-Me and cytidine or thymidine is more thermodynamically favorable than with adenosine and guanosine. However, differences in the melting temperature and DeltaG degrees 's of 8-oxoG/dC and 8-oxoG/T were much smaller than between G/dC and G/T. CD spectra showed that DNA . RNA containing 8-oxoG or 8-oxoG-Me duplexes showed similarities between the A-type RNA and B-type DNA conformations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing*
  • Circular Dichroism
  • DNA / chemistry*
  • Genomic Instability
  • Guanosine / analogs & derivatives*
  • Guanosine / chemistry
  • Guanosine / genetics
  • Molecular Structure
  • Nucleic Acid Conformation*
  • Nucleic Acid Heteroduplexes / chemistry*
  • Nucleic Acid Heteroduplexes / genetics
  • Oligonucleotides / chemistry
  • Oligonucleotides / genetics
  • RNA / chemistry*
  • Thermodynamics

Substances

  • 8-oxo-7,8-dihydro-2'-O-methylguanosine
  • Nucleic Acid Heteroduplexes
  • Oligonucleotides
  • Guanosine
  • 8-hydroxyguanosine
  • RNA
  • DNA