title: Selective inhibition of the 3'-to-5' exonuclease activity associated with Epstein-Barr virus DNA polymerase by ribonucleoside 5'-monophosphates.
abstract: Epstein-Barr virus (EBV) DNA polymerase possesses a proofreading 3'-to-5' exonuclease activity (Tsurumi, T. (1991) Virology 182, 376-381). The 3'-to-5' exonuclease activity can be selectively inhibited by ribonucleoside 5'-monophosphates, while no inhibition of the DNA polymerase activity can be observed even when the template/primer concentrations are rate-limiting. Deoxynucleoside monophosphates except 5'dGMP have almost no effect on the exonuclease activity. Of the four ribonucleoside monophosphates, 5'GMP is the most potent (62% inhibition at 5 mM). The kinetic study shows that 5'-GMP inhibits the exonuclease activity competitively with respect to DNA template/primer. During DNA polymerization process the EBV DNA polymerase catalyzes the DNA-dependent conversion of complementary deoxynucleoside triphosphate to monophosphate form. With poly(dT).oligo(rA) as a template primer, selective inhibition of the exonuclease activity by 5'-GMP results in a decrease in the amount of free dAMP generated which is complementary to the template DNA, suggesting the functional relationship between the editing exonuclease activity and the chain elongation activity of the EBV DNA polymerase molecule.
authors.affiliation: Laboratory of Virology, Nagoya University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tsurumi
mesh_terms: D004926:Escherichia coli / Q000201:enzymology; D005092:Exonucleases / Q000037:antagonists & inhibitors*; D004854:Herpesvirus 4, Human / Q000201:enzymology*; D007700:Kinetics; D019384:Nucleic Acid Synthesis Inhibitors; D012265:Ribonucleotides / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D012265:Ribonucleotides; D005092:Exonucleases