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Nucleic Acids Symposium Series 2000 44(1):71-72; doi:10.1093/nass/44.1.71
© 2000 by Oxford University Press
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Retrovirus-specific random mutagenesis by a nucleoside 5'-triphosphate analogue, PTP

Kei Moriyama1, Toshiyuki Okada1, David Loakes2 and Kazuo Negishi1

1 Gene Research Center, Okayama University, Tsushima, Okayama 700-8530, Japan, 2 Medical Research Council,Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK

In a retrovirus replication model system, which consists of in vitro transcription and reverse transcription cycles, 6-(ß-D-ribofuranosyl)-3,4-dihydro-8H-pyrimido[4,5-c][1,2]oxazin-7-one-5'-triphosphate (PTP) induced highly efficient random mutations and this was due to the ambiguous incorporation of PTP by RNA polymerases. The types of mutations were mainly C-to-U or U-to-C transition mutations and the frequency was about 4 x 10–2/nucleotide during four cycles of the replication. Since a high mutation rate is harmful to species, PTP may be new candidate for anti-retroviral drugs. N4-aminoCTP and N4-hydroxyCTP were also incorporated ambiguously by RNA polymerase. These compounds may have a potential to induce mutation by the same mechanism as PTP.


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