Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues

Nature. 1987 May 7-13;327(6117):77-9. doi: 10.1038/327077a0.

Abstract

It has been shown previously that deoxyguanosine residues in DNA are hydroxylated at the C-8 position both in vitro and in vivo to produce 8-hydroxydeoxyguanosine (8-OH-dG) by various agents that produce oxygen radicals such as reducing reagents-O2, metal ions-O2, polyphenol-H2O2-Fe3+, asbestos-H2O2 or ionizing radiation. These agents are mostly either mutagenic or carcinogenic; therefore, the formation of 8-OH-dG can also be considered a likely cause of mutation or carcinogenesis by oxygen radicals. It is of interest to know whether the 8-OH-dG residue in DNA is misread during DNA replication. To answer this question, we have examined the effect of the 8-OH-dG residue in DNA on the fidelity of DNA replication using a DNA synthesis system in vitro with Escherichia coli DNA polymerase I (Klenow fragment). The synthetic oligodeoxynucleotides, with or without an 8-OH-dG residue in a specified position, were chemically synthesized and used as templates for DNA synthesis under the conditions of the dideoxy chain termination sequencing method. Surprisingly, in addition to misreading of the 8-OH-dG residue itself, pyrimidines next to the 8-OH-dG residue (G has not yet been tested) were also misread.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Base Sequence
  • DNA / drug effects
  • DNA / genetics*
  • DNA Damage
  • DNA Replication
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / genetics
  • Free Radicals
  • Mutation*
  • Oxygen / pharmacology
  • Templates, Genetic*

Substances

  • Free Radicals
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • Deoxyguanosine
  • Oxygen