Comparisons of the fidelity of transcription of RNA polymerase I and II following N-hydroxy-2-acetylaminofluorene treatment

Abstract

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.