The 5'-triphosphates of 3'-azido-3'-deoxythymidine and 2', 3'-dideoxynucleosides inhibit DNA polymerase gamma by different mechanisms.
Inhibition mechanisms of 5'-triphosphates of 3'-azido-3'-deoxythymidine (AZT-TP) and 3'-deoxythymidine (ddTTP) on extensively purified DNA polymerase gamma from bovine testes were examined by analysis of the products synthesized on singly primed M13 single-stranded DNA or synthetic oligonucleotide template-primer in the presence of analogues. The results indicate that AZT-TP inhibits DNA polymerase gamma in competition with dTTP but is not incorporated into DNA, whereas ddTTP is incorporated into DNA and causes chain termination. In contrast, both analogues were used by reverse transcriptase and caused chain termination.
Izuta
S
S
Laboratory of Cancer Cell Biology, Nagoya University School of Medicine, Japan.
Saneyoshi
M
M
Sakurai
T
T
Suzuki
M
M
Kojima
K
K
Yoshida
S
S
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D002417:Cattle; D004258:DNA Polymerase III / Q000037:antagonists & inhibitors*; D004277:DNA, Single-Stranded / Q000378:metabolism; D015224:Dideoxynucleosides / Q000494:pharmacology*; D054306:Dideoxynucleotides; D004591:Electrophoresis, Polyacrylamide Gel; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000378:metabolism; D013737:Testis / Q000201:enzymology; D013942:Thymine Nucleotides / Q000494:pharmacology*; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000998:Antiviral Agents; D004277:DNA, Single-Stranded; D015224:Dideoxynucleosides; D054306:Dideoxynucleotides; D009841:Oligonucleotides; D013942:Thymine Nucleotides; C019336:2',3'-dideoxythymidine; D015215:Zidovudine; C052873:zidovudine triphosphate; D004258:DNA Polymerase III