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Effect of heliquinomycin on the activity of human minichromosome maintenance 4/6/7 helicase
Author(s) -
Ishimi Yukio,
Sugiyama Takafumi,
Nakaya Ryou,
Kanamori Makoto,
Kohno Toshiyuki,
Enomoto Takemi,
Chino Makoto
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07064.x
Subject(s) - minichromosome maintenance , helicase , primase , dna polymerase , dna , dna replication , minichromosome , biology , microbiology and biotechnology , rna helicase a , circular bacterial chromosome , chemistry , biochemistry , eukaryotic dna replication , rna , gene , chromatin , reverse transcriptase
The antibiotic heliquinomycin, which inhibits cellular DNA replication at a half‐maximal inhibitory concentration (IC 50 ) of 1.4–4 μ m , was found to inhibit the DNA helicase activity of the human minichromosome maintenance (MCM) 4/6/7 complex at an IC 50 value of 2.4 μ m . In contrast, 14 μ m heliquinomycin 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 IC 50 values of 25 and 6.5 μ m , heliquinomycin inhibited the RNA priming and DNA polymerization activities, respectively, of human DNA polymerase‐α/primase. Thus, of the enzymes studied, the MCM4/6/7 complex was the most sensitive to heliquinomycin; 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 IC 50 value of 5.2 μ m inhibited the ATPase activity of the MCM4/6/7 complex in the presence of single‐stranded DNA. This suggests that heliquinomycin interferes with the interaction of the MCM4/6/7 complex with single‐stranded DNA.