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Incorporation of 8-hydroxyguanosine (8-oxo-7,8-dihydroguanosine) 5'-triphosphate by bacterial and human RNA polymerases

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Title: Incorporation of 8-hydroxyguanosine (8-oxo-7,8-dihydroguanosine) 5'-triphosphate by bacterial and human RNA polymerases
Other Titles: Incorporation of 8-hydroxyguanosine 5'-triphosphate (8-oxo-7,8-dihydroguanosine 5'-triphosphate) by bacterial and human RNA polymerases
Authors: Kamiya, Hiroyuki Browse this author
Suzuki, Akihiro Browse this author
Yamaguchi, Yuki Browse this author
Handa, Hiroshi Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: Oxidized ribonucleotide
8-Hydroxyguanosine 5'-triphosphate
RNA polymerase
Transcription
Free radicals
Issue Date: 15-Jun-2009
Publisher: Elsevier Inc.
Journal Title: Free Radical Biology and Medicine
Volume: 46
Issue: 12
Start Page: 1703
End Page: 1707
Publisher DOI: 10.1016/j.freeradbiomed.2009.04.005
PMID: 19362141
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 call cause the formation of oxidized RNA and disturb the transmittance of genetic information.
Type: article (author version)
URI: http://hdl.handle.net/2115/38630
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 紙谷 浩之

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