10.1021/tx0601455.s001 James S. Stover James S. Stover Goutam Chowdhury Goutam Chowdhury Hong Zang Hong Zang F. Peter Guengerich F. Peter Guengerich Carmelo J. Rizzo Carmelo J. Rizzo Translesion Synthesis Past the C8- and <i>N</i><sup>2</sup>-Deoxyguanosine Adducts of the Dietary Mutagen 2-Amino-3-methylimidazo[4,5-<i>f</i>]quinoline in the <i>Nar</i>I Recognition Sequence by Prokaryotic DNA Polymerases American Chemical Society 2006 tandem mass spectrometry dGuo Dpo 1G noniterated sequences result extension frameshift mutations Escherichia coli pol Sulfolobus solfataricus P 2 DNA polymerase IV NarI Recognition Sequence forms DNA adducts IQ II replication exo 2006-11-20 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Translesion_Synthesis_Past_the_C8_and_i_N_i_sup_2_sup_Deoxyguanosine_Adducts_of_the_Dietary_Mutagen_2_Amino_3_methylimidazo_4_5_i_f_i_quinoline_in_the_i_Nar_i_I_Recognition_Sequence_by_Prokaryotic_DNA_Polymerases/3047194 2-Amino-3-methylimidazo[4,5-<i>f</i>]quinoline (IQ) is found in cooked meats and forms DNA adducts at the C8- and <i>N</i><sup>2</sup>-positions of dGuo after appropriate activation. IQ is a potent inducer of frameshift mutations in bacteria and is carcinogenic in laboratory animals. We have incorporated both IQ-adducts into the G<sub>1</sub>- and G<sub>3</sub>-positions of the <i>Nar</i>I recognition sequence (5‘-G<sub>1</sub>G<sub>2</sub>CG<sub>3</sub>CC-3‘), which is a hotspot for arylamine modification. The in vitro replication of the oligonucleotides was examined with <i>Escherichia coli</i> pol I Klenow fragment exo<sup>-</sup>, <i>E. coli</i> pol II exo<sup>-</sup>, and <i>Sulfolobus solfataricus</i> P2 DNA polymerase IV (Dpo4), and the extension products were sequenced by tandem mass spectrometry. Replication of the C8-adduct at the G<sub>3</sub>-position resulted in two-base deletions with all three polymerases, whereas error-free bypass and extension was observed at the G<sub>1</sub>-position. The <i>N</i><sup>2</sup>-adduct was bypassed and extended by all three polymerases when positioned at the G<sub>1</sub>-position, and the error-free product was observed. The <i>N</i><sup>2</sup>-adduct at the G<sub>3</sub>-position was more blocking and was bypassed and extended only by Dpo4 to produce an error-free product. These results indicate that the replication of the IQ-adducts of dGuo is strongly influenced by the local sequence and the regioisomer of the adduct. These results also suggest a possible role for pol II and IV in the error-prone bypass of the C8-IQ-adduct leading to frameshift mutations in reiterated sequences, whereas noniterated sequences result in error-free bypass.