2-Aminofluorene modified DNA duplex exists in two interchangeable conformations.
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.
Eckel
L M
LM
Department of Chemistry, University of Rochester, New York 14627, USA.
Krugh
T R
TR
D001483:Base Sequence; D001665:Binding Sites; D002273:Carcinogens / Q000737:chemistry; D003062:Codon / Q000737:chemistry / Q000235:genetics; D018736:DNA Adducts / Q000737:chemistry*; D005449:Fluorenes / Q000737:chemistry*; D011905:Genes, ras; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016296:Mutagenesis; D009690:Nucleic Acid Conformation; D000090063:Proto-Oncogene Mas; D013816:Thermodynamics
C052668:2-aminofluorene-DNA complex; D002273:Carcinogens; D003062:Codon; D018736:DNA Adducts; D005449:Fluorenes; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas