Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidation of RNA precursors may disturb genetic information by mispair formations. In this study, effects of oxidized ribonucleoside triphosphates on in vitro transcription catalyzed by T7 RNA polymerase were examined. 8-Hydroxyguanosine 5'-triphosphate (8-OH-GTP) and 2-hydroxyadenosine 5'-triphosphate (2-OH-ATP) reduced amount of RNA. In addition, mRNA was converted to cDNA by reverse transcriptase, and the cDNA was then amplified by PCR. The PCR product was subsequently cloned into plasmid DNA and sequence of DNA was analyzed for each bacterial colony. The two oxidized ribonucleotides induced mutations in cDNA, suggesting disturbance of genetic information during transcription and/or reverse transcription. 8-OH-GTP induced T-->G plus T-->C mutations and 2-OH-ATP caused T-->C mutations. These results indicate that formation of these oxidized RNA precursors in cells affects transcription quantitatively and qualitatively. In addition, they are potential antiviral drugs that cause mutations in genomic RNA.
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PMID:Mutagenic properties of oxidized GTP and ATP in in vitro transcription-reverse transcription. 1715 Aug 36

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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PMID:Incorporation of 8-hydroxyguanosine (8-oxo-7,8-dihydroguanosine) 5'-triphosphate by bacterial and human RNA polymerases. 1936 41