Incorporation of 8-hydroxyguanosine (8-oxo-7,8-dihydroguanosine) 5′-triphosphate by bacterial and human RNA polymerases |
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Authors: | Hiroyuki Kamiya Akihiro Suzuki Yuki Yamaguchi Hiroshi Handa Hideyoshi Harashima |
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Institution: | aFaculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan;bGraduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan |
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Abstract: | Oxidized RNA precursors formed in the nucleotide pool may be incorporated into RNA. In this study, the incorporation of 8-hydroxyguanosine 5′-triphosphate (8-OH-GTP; 8-oxo-7,8-dihydroguanosine 5′-triphosphate) into RNA by Escherichia coli RNA polymerase was examined in vitro, using a primer RNA and a template DNA with defined sequences. 8-OH-GTP was incorporated opposite C and A in the template DNA. Surprisingly, 8-OH-GTP was quite efficiently incorporated by the bacterial RNA polymerase, in contrast to the incorporation of the 2′-deoxyribo counterpart by DNA polymerases, as indicated by the kinetic parameters. The primer was further extended by the addition of a ribonucleotide complementary to the nucleobase adjacent to C or A (the nucleobase opposite which 8-OH-GTP was inserted). Thus, the incorporation of 8-OH-GTP did not completely inhibit further RNA chain elongation. 8-OH-GTP was also incorporated opposite C and A by human RNA polymerase II. These results suggest that 8-OH-GTP in the nucleotide pool can cause the formation of oxidized RNA and disturb the transmittance of genetic information. |
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