2-Aminofluorene modified DNA duplex exists in two interchangeable conformations

Nat Struct Biol. 1994 Feb;1(2):89-94. doi: 10.1038/nsb0294-89.

Abstract

One- and two-dimensional NMR shows that the carcinogen 2-aminofluorene exists in two unique, interchangeable conformations when covalently bound to a model human c-H-ras1 proto-oncogene codon 61 oligomer duplex. In one conformation the 2-aminofluorene moiety protrudes out of the major groove leaving the Watson-Crick base pairing of the cytosine and 2-aminofluorene-guanine bases intact, consistent with the ability of replicating enzymes to bypass the lesion and correctly incorporate cytosine. The second form of the modified oligomer duplex may be representative of a pre-mutagenic conformation in that the 2-aminofluorene moiety is stacked within the DNA helix, disrupting base pairing between the 2-aminofluorene-modified guanine and its complementary cytosine.

Publication types

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

MeSH terms

  • Base Sequence
  • Binding Sites
  • Carcinogens / chemistry
  • Codon / chemistry
  • Codon / genetics
  • DNA Adducts / chemistry*
  • Fluorenes / chemistry*
  • Genes, ras
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Mutagenesis
  • Nucleic Acid Conformation
  • Proto-Oncogene Mas
  • Thermodynamics

Substances

  • 2-aminofluorene-DNA complex
  • Carcinogens
  • Codon
  • DNA Adducts
  • Fluorenes
  • MAS1 protein, human
  • Proto-Oncogene Mas