Incorporation of oxidized guanine nucleoside 5'-triphosphates in DNA with DNA polymerases and preparation of single-lesion carrying DNA

Biochemistry. 2008 Apr 22;47(16):4788-99. doi: 10.1021/bi7022199. Epub 2008 Mar 28.

Abstract

We investigated the incorporation of oxidatively modified guanine residues in DNA using three DNA polymerases, Escherichia coli Kf exo+, Kf exo-, and Taq DNA polymerase. We prepared nucleoside 5'-triphosphates with modified bases (dN (ox)TP) including imidazolone associated with oxazolone (dIzTP/dZTP), dehydroguanidinohydantoin (dOGhTP), and oxaluric acid (dOxaTP). We showed that the single-nucleotide incorporation of these dN (ox)TP at the 3'-end of a primer DNA strand was possible opposite C or G for dIzTP/dZTP, opposite C for dOGhTP using the Klenow fragment, and opposite C for dOxaTP using Taq. The efficiency of these misincorporations was compared to that of the nucleoside 5'-triphosphate modified with the mutagenic guanine lesion 8-oxo-G opposite A or C as well as to that of the natural dNTPs. The reaction was found not competitive. However, the ability of Kf exo- to further copy the whole template DNA strand from the primer carrying one modified residue at the 3'-end proved to be easy and rapid. The two-step polymerization process consisting of the single-nucleotide extension followed by the full extension of a primer afforded a method for the preparation of tailored double-stranded DNA oligonucleotides carrying a single modified base at a precise site on any sequence. This very rapid method allowed the incorporation of unique residues in DNA that were not available before due to their unstable character.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / metabolism*
  • DNA-Directed DNA Polymerase / metabolism*
  • Guanosine Triphosphate / chemistry*
  • Guanosine Triphosphate / metabolism*
  • Molecular Structure
  • Oxidation-Reduction

Substances

  • Guanosine Triphosphate
  • DNA
  • DNA-Directed DNA Polymerase