caa a22 4500 397556152 CHVBK 20180308164802.0 cr unu---uuuuu 161202e199606 xx s 000 0 eng 10.1093/oxfordjournals.jbchem.a021345 doi (NATIONALLICENCE)oxford-10.1093/oxfordjournals.jbchem.a021345 3′-Deoxyribonucleotides Inhibit Eukaryotic DNA Primase [Elektronische Daten] [Shunji Izuta, Mizue Kohsaka-Ichikawa, Toyofumi Yamaguchi, Mineo Saneyosh] In order to elucidate the biological activities of cordycepin (3′-deoxyadenosine) and related 3′-deoxyribonucleosides on eukaryotic DNA replication, the inhibitory effects of triphosphate derivatives of 3′-deoxyadenosine (3′-dATP), 8-azido-3′-deoxyadenosine (8-N3-3′-dATP), 3′-deoxyguanosine (3′-dGTP), 3′-deoxyuridine (3′-dUTP), 5-fluoro-3′-deoxyuridine (5-F-3′-dUTP), 3′-deoxycytidine (3′-dCTP), and 5-fluoro-3′-deoxycytidine (5-F-3′-dCTP) on DNA primase and replicative DNA polymerases α, δ, and ε purified from cherry salmon (Oncorhynchus masou) testes or calf thymus were examined. All analogs, except 8-N3-3′-dATP, showed strong inhibitory effects on DNA primase, but none of them inhibited DNA polymerases α, δ, or ε. Kinetic analysis revealed that the inhibition modes of them were competitive with respect to the incorporation of natural substrate that had the corresponding base moiety and non-competitive with respect to other substrates. Based on the kinetic data, we compared the affinities of 3′-dNTPs between DNA primase and RNA polymerases I and II, since 3′-dNTPs also inhibit eukaryotic RNA polymerases. Although the K1 values for DNA primase were much larger than those for RNA polymerases, the K1/Km values, which indicate the affinity of the analog to the enzyme, were very similar. © by the Journal of Biochemistry Regular Papers nationallicence cherry salmon nationallicence DNA polymerase α family nationallicence DNA primase nationallicence 3′-deoxyribonucleotides nationallicence synthetic inhibitor nationallicence Izuta Shunji Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine Showa-ku, Nagoya 466 aut Kohsaka-Ichikawa Mizue Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Showa-ku, Nagoya 466, Uenohara-machi, Kitatsuru-gun, Yamanashi 409-01 aut Yamaguchi Toyofumi Department of Biological Sciences, The Nishi-Tokyo University Uenohara-machi, Kitatsuru-gun, Yamanashi 409-01 aut Saneyosh Mineo Department of Biological Sciences, The Nishi-Tokyo University Uenohara-machi, Kitatsuru-gun, Yamanashi 409-01 aut The Journal of Biochemistry Oxford University Press 119/6(1996-06), 1038-1044 0021-924X 119:6<1038 1996 119 jbchem https://doi.org/10.1093/oxfordjournals.jbchem.a021345 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/oxfordjournals.jbchem.a021345 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Izuta Shunji Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine Showa-ku, Nagoya 466 aut NATIONALLICENCE 700 1- Kohsaka-Ichikawa Mizue Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Showa-ku, Nagoya 466, Uenohara-machi, Kitatsuru-gun, Yamanashi 409-01 aut NATIONALLICENCE 700 1- Yamaguchi Toyofumi Department of Biological Sciences, The Nishi-Tokyo University Uenohara-machi, Kitatsuru-gun, Yamanashi 409-01 aut NATIONALLICENCE 700 1- Saneyosh Mineo Department of Biological Sciences, The Nishi-Tokyo University Uenohara-machi, Kitatsuru-gun, Yamanashi 409-01 aut NATIONALLICENCE 773 0- The Journal of Biochemistry Oxford University Press 119/6(1996-06), 1038-1044 0021-924X 119:6<1038 1996 119 jbchem Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford