Chain Termination With Sugar- Modified Nucleotide Analogs in the DNA Synthesis by DNA Polymerase γ

We examined the effects of sugar-modified nucleotide analogs on the reaction with DNA polymerase γ and HIV reverse transcriptase. The 3′-modified derivative, 3′-amino-3′-deoxythymidine 5′-triphosphate inhibited the reaction of both enzymes. However, where it did not cause chain termination in the DNA polymerase y reaction, it did cause termination in HIV reverse transcriptase reaction. On the other hand, the triphosphate derivative of oxetanocin G which has a 3, 4-dihydroxymethyloxetane at the sugar moiety instead of ribofuranose showed the chain termination in both polymerase reactions, however, termination sites with DNA polymerase γ reaction were different from those with HIV reverse transcriptase or with DNA polymerase α. These results, combined with our previous data, indicate that the action of several sugar-modified nucleotide analogs on DNA polymerase γ could be very different from those on other eukaryotic DNA polymerases including HIV reverse transcriptase. 1. This paper is dedicated to Dr. Yoshihisa Mizuno on the occasion of his 75th birthday.