Biochemical studies on the mutagen, 6-N-hydroxylaminopurine. Synthesis of the deoxynucleoside triphosphate and its incorporation into DNA in vitro

J Biol Chem. 1986 Feb 15;261(5):2020-6.

Abstract

The nucleotide analogue, 6-N-hydroxylaminopurine deoxynucleoside triphosphate (dHAPTP) has been synthesized from 6-chloropurine by a procedure involving both enzymatic and chemical reagents. In a series of experiments involving several different DNA polymerases including 3 procaryotic and 2 eucaryotic enzymes, it was shown that dHAPTP is ambiguous in its base-pairing characteristics, since it can replace both dATP and dGTP in DNA synthesis. It was also shown that different enzymes have different capacities to distinguish dHAPTP from the canonical deoxynucleoside triphosphates. These results are consistent with (but do not prove) the hypothesis that the mechanism of 6-N-hydroxylaminopurine mutagenesis seen in both eucaryotic and procaryotic organisms is due to its conversion, in vivo, to a deoxynucleoside triphosphate which is incorporated ambiguously for dATP and dGTP during DNA replication.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / metabolism
  • DNA / biosynthesis
  • DNA-Directed DNA Polymerase / metabolism
  • Deoxyadenine Nucleotides / chemical synthesis
  • Deoxyadenine Nucleotides / metabolism*
  • Eukaryotic Cells / enzymology
  • Molecular Conformation
  • Mutagens / metabolism
  • Prokaryotic Cells / enzymology
  • Substrate Specificity

Substances

  • Deoxyadenine Nucleotides
  • Mutagens
  • 6-N-hydroxylaminopurine deoxynucleoside triphosphate
  • 6-N-hydroxylaminopurine
  • DNA
  • DNA-Directed DNA Polymerase
  • Adenine