Comparisons of the fidelity of transcription of RNA polymerase I and II following N-hydroxy-2-acetylaminofluorene treatment.
Using hepatic RNA polymerase I and II from either normal or N-2-hydroxy-2-acetylaminofluorene (N-OH-AAF)-treated rats or E. coli RNA polymerase, the degree of misincorporation of noncomplementary nucleotides was assessed with the synthetic templates, poly(dG-dC).poly(dG-dC) and poly (dA-dT).poly(dA-dT). The predominant base-pair transformation that was transcribed in the presence of Mg++ or Mn++ by RNA polymerase I from control or N-OH-AAF-treated animals or by E. coli RNA polymerase with poly(dG-dC).poly(dG-dC) as template was the transversion, dG-rC to dG-rA; however, transcription in the presence of Mg++ by RNA polymerase II from carcinogen-treated animals showed a statistically greater degree of the base-pair transformation, dG-rC to dG-rU. In contrast, RNA polymerase I and II from control or N-OH-AAF-treated animals transcribed the base-pair transformation, dA-rU to dA-rG, dA-rU to dA-rC and dA-rU to dA-rA to equal extents with poly(dA-dT).poly(dA-dT) as template. E. coli RNA polymerase transcribed the latter template to produce only the transversion, dA-rU to dA-rG. These results suggest that RNA polymerases are capable of miscopying synthetic DNA templates. The consequences of base-pair transformations on the fidelity of transcription after carcinogen treatment is discussed.
D000818:Animals; D001483:Base Sequence; D002413:Cations, Divalent / Q000494:pharmacology; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D005449:Fluorenes / Q000494:pharmacology*; D006881:Hydroxyacetylaminofluorene / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008297:Male; D011089:Polydeoxyribonucleotides / Q000378:metabolism; D012318:RNA Polymerase I / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism*; D051381:Rats; D013698:Templates, Genetic; D014158:Transcription, Genetic / Q000187:drug effects*
D002413:Cations, Divalent; D005449:Fluorenes; D011089:Polydeoxyribonucleotides; D006881:Hydroxyacetylaminofluorene; D012319:RNA Polymerase II; D012321:DNA-Directed RNA Polymerases; D012318:RNA Polymerase I