Retrovirus-specific random mutagenesis by a nucleoside 5'-triphosphate analogue, PTP.
In a retrovirus replication model system, which consists of in vitro transcription and reverse transcription cycles, 6-(beta-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.
Moriyama
K
K
Gene Research Center, Okayama University, Tsushima, Okayama 700-8530, Japan.
Okada
T
T
Loakes
D
D
Negishi
K
K
D016296:Mutagenesis; D009153:Mutagens / Q000737:chemistry / Q000494:pharmacology; D012190:Retroviridae / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D012265:Ribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000235:genetics
C476366:6-(2-ribofuranosyl)-3,4-dihydro-8H-pyrimido(4,5-c)(1,2)oxazin-7-one 5'-triphosphate; D009153:Mutagens; D012265:Ribonucleotides