Mutagenic properties of ribonucleotide analogues in reverse transcription with HIV and AMV reverse transcriptases.
Pyrimidine analogues, N4-hydroxycytosine (C(oh)), N4-methoxycytosine (C(mo)) and 6H, 8H-3,4-dihydropyrimido[4,5-c][1,2]oxazin-7-one (P) can form base pairs with both adenine and guanine. We examined the mutagenic properties of these ribonucleotide analogues in RNA in reverse transcription with HIV and AMV reverse transcriptases. Both reverse transcriptases incorporated dATP and dGTP opposite these analogues in RNA. The incorporation ratio of dGTP to dATP opposite each analogue was measured to estimate the potential for inducing U-to-C mutations. The potentials may be rC(oh) > rC(mo) > rP for both reverse transcriptases. It might be possible to induce mutations in the retroviral genomes and to develop a new antiviral therapy, if these analogues are incorporated by a human RNA polymerase.
Suzuki
Tetsuya
T
Department of Genomics and Proteomics, Okayama University Advanced Science Research Center, Tsushima, Okayama 700-8530, Japan.
Okada
Toshiyuki
T
Otsuka
Chie
C
Moriyama
Kei
K
Loakes
David
D
Negishi
Kazuo
K
D009189:Avian Myeloblastosis Virus / Q000201:enzymology; D020029:Base Pairing; D002851:Chromatography, High Pressure Liquid; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006678:HIV / Q000201:enzymology; D009154:Mutation; D010078:Oxazines / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D048348:Reverse Transcription
D010078:Oxazines; D011743:Pyrimidines; C062254:6H,8H-3,4-dihydropyrimido(4,5-c)(1,2)oxazin-7-one; C021202:N(4)-hydroxycytosine; C036689:N(4)-methoxycytosine; D003596:Cytosine; D012194:RNA-Directed DNA Polymerase