tailieunhanh - Báo cáo khoa học: Effect of heliquinomycin on the activity of human minichromosome maintenance 4/6/7 helicase

The antibiotic heliquinomycin, which inhibits cellular DNA replication at a half-maximal inhibitory concentration (IC50) of –4lm, was found to inhi-bit the DNA helicase activity of the human minichromosome maintenance (MCM) 4/6/7 complex at an IC50value of . In contrast, 14 lmheliqui-nomycin did not inhibit significantly either the DNA helicase activity of the SV40 T antigen and Werner protein or the oligonucleotide displacement activity of human replication protein A. | Effect of heliquinomycin on the activity of human minichromosome maintenance 4 6 7 helicase Yukio Ishimi1 2 Takafumi Sugiyama1 Ryou Nakaya1 Makoto Kanamori3 Toshiyuki Kohno2 Takemi Enomoto3 and Makoto Chino4 1 College of Science Ibaraki University Japan 2 Macromolecular Structure Research Group Mitsubishi Kagaku Institute of Life Sciences Tokyo Japan 3 Molecular CellBiology Laboratory Graduate Schoolof PharmaceuticalSciences Tohoku University Miyagi Japan 4 Pharmaceuticals Group Nippon Kayaku Co. Ltd. Tokyo Japan Keywords anticancer drug DNA replication MCM 4 6 7 helicase Correspondence Y. Ishimi Ibaraki University 2-1-1 Bunkyo Mito Ibaraki 310-8512 Japan Fax 81 29 228 8439 Tel 81 29 228 8439 E-mail ishimi@ Received 9 March 2009 revised 13 April 2009 accepted 16 April 2009 doi The antibiotic heliquinomycin which inhibits cellular DNA replication at a half-maximal inhibitory concentration IC50 of pM was found to inhibit the DNA helicase activity of the human minichromosome maintenance MCM 4 6 7 complex at an IC50 value of pM. In contrast 14 IM heliqui-nomycin did not inhibit significantly either the DNA helicase activity of the SV40 T antigen and Werner protein or the oligonucleotide displacement activity of human replication protein A. At IC50 values of 25 and pM heliquinomycin inhibited the RNA priming and DNA polymerization activities respectively of human DNA polymerase-a primase. Thus of the enzymes studied the MCM4 6 7 complex was the most sensitive to heliqui-nomycin this suggests that MCM helicase is one of the main targets of heliquinomycin in vivo. It was observed that heliquinomycin did not inhibit the ATPase activity of the MCM4 6 7 complex to a great extent in the absence of single-stranded DNA. In contrast heliquinomycin at an IC50 value of M inhibited the ATPase activity of the MCM4 6 7 complex in the presence of single-stranded DNA. This suggests that heliquinomycin interferes with .

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