Interactions between DNA polymerase and aminofluorene adducts that affect the recognition and possibly the mutagenicity of the lesions.
Adducts of 2-aminofluorene on the C-8 position of guanine block DNA synthesis and lead to mutation. N-acetylated adducts adopt the syn conformation such that in DNA the guanine is displaced from the helix by the fluorene ring while unacetylated adducts prefer the anti conformation allowing normal base pairing of the guanine with cytosine. In vitro synthesis by both E. coli DNA polymerase I and T4 DNA polymerase terminates predominantly one nucleotide before acetylated adducts but has an increased tendency to terminate opposite the unacetylated adducts apparently reflecting the preferred conformations of the two species of reacted nucleoside. In complete contrast AMV reverse transcriptase correctly inserts cytosine opposite the acetylated adducts but prefers to terminate one nucleotide before the unacetylated adducts. We interpret these results as indicating that the specific properties of a replicating polymerase can influence the conformation of a reacted nucleoside thus altering its recognition and possibly its mutagenic activity.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000099:Acetoxyacetylaminofluorene / Q000378:metabolism* / Q000494:pharmacology; D009189:Avian Myeloblastosis Virus / Q000201:enzymology; D010584:Bacteriophage phi X 174; D004256:DNA Polymerase I / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013604:T-Phages / Q000201:enzymology; D013698:Templates, Genetic
D004279:DNA, Viral; D000099:Acetoxyacetylaminofluorene; D015073:2-Acetylaminofluorene; D012194:RNA-Directed DNA Polymerase; D004256:DNA Polymerase I; D004259:DNA-Directed DNA Polymerase