Interaction of heliquinomycin with single-stranded DNA inhibits MCM4/6/7 helicase

Takafumi Sugiyama, Makoto Chino, Toshiki Tsurimoto, Naohito Nozaki, Yukio Ishimi

研究成果: ジャーナルへの寄稿記事

11 引用 (Scopus)

抄録

The antibiotic heliquinomycin inhibited cellular DNA replication at IC50 of 2.5 M without affecting level of chromatin-bound MCM4 and without activating the DNA replication stress checkpoint system, suggesting that heliquinomycin perturbs DNA replication mainly by inhibiting the activity of replicative DNA helicase that unwinds DNA duplex at replication forks. Among the DNA helicases involved in DNA replication, DNA helicase B was inhibited by heliquinomycin at IC50 of 4.3 M and RECQL4 helicase at IC50 of 14 M; these values are higher than that of MCM4/6/7 helicase (2.5 M). These results suggest that heliquinomycin mainly targets actions of the replicative DNA helicases. Gel-retardation experiment indicates that heliquinomycin binds to single-stranded DNA. The single-stranded DNA-binding ability of MCM4/6/7 was affected in the presence of heliquinomycin. The data suggest that heliquinomycin inhibits the DNA helicase activity of MCM4/6/7 complex by stabilizing its interaction with single-stranded DNA. The Authors 2011. Published by Oxford University Press on behalf of the Japanese Biochemical Society.

元の言語英語
ページ(範囲)129-137
ページ数9
ジャーナルJournal of Biochemistry
151
発行部数2
DOI
出版物ステータス出版済み - 2 1 2012

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Single-Stranded DNA
DNA Helicases
DNA Replication
DNA
Inhibitory Concentration 50
heliquinomycin
Chromatin
Gels
Anti-Bacterial Agents

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

これを引用

Interaction of heliquinomycin with single-stranded DNA inhibits MCM4/6/7 helicase. / Sugiyama, Takafumi; Chino, Makoto; Tsurimoto, Toshiki; Nozaki, Naohito; Ishimi, Yukio.

:: Journal of Biochemistry, 巻 151, 番号 2, 01.02.2012, p. 129-137.

研究成果: ジャーナルへの寄稿記事

Sugiyama, Takafumi ; Chino, Makoto ; Tsurimoto, Toshiki ; Nozaki, Naohito ; Ishimi, Yukio. / Interaction of heliquinomycin with single-stranded DNA inhibits MCM4/6/7 helicase. :: Journal of Biochemistry. 2012 ; 巻 151, 番号 2. pp. 129-137.
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abstract = "The antibiotic heliquinomycin inhibited cellular DNA replication at IC50 of 2.5 M without affecting level of chromatin-bound MCM4 and without activating the DNA replication stress checkpoint system, suggesting that heliquinomycin perturbs DNA replication mainly by inhibiting the activity of replicative DNA helicase that unwinds DNA duplex at replication forks. Among the DNA helicases involved in DNA replication, DNA helicase B was inhibited by heliquinomycin at IC50 of 4.3 M and RECQL4 helicase at IC50 of 14 M; these values are higher than that of MCM4/6/7 helicase (2.5 M). These results suggest that heliquinomycin mainly targets actions of the replicative DNA helicases. Gel-retardation experiment indicates that heliquinomycin binds to single-stranded DNA. The single-stranded DNA-binding ability of MCM4/6/7 was affected in the presence of heliquinomycin. The data suggest that heliquinomycin inhibits the DNA helicase activity of MCM4/6/7 complex by stabilizing its interaction with single-stranded DNA. The Authors 2011. Published by Oxford University Press on behalf of the Japanese Biochemical Society.",
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AU - Chino, Makoto

AU - Tsurimoto, Toshiki

AU - Nozaki, Naohito

AU - Ishimi, Yukio

PY - 2012/2/1

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N2 - The antibiotic heliquinomycin inhibited cellular DNA replication at IC50 of 2.5 M without affecting level of chromatin-bound MCM4 and without activating the DNA replication stress checkpoint system, suggesting that heliquinomycin perturbs DNA replication mainly by inhibiting the activity of replicative DNA helicase that unwinds DNA duplex at replication forks. Among the DNA helicases involved in DNA replication, DNA helicase B was inhibited by heliquinomycin at IC50 of 4.3 M and RECQL4 helicase at IC50 of 14 M; these values are higher than that of MCM4/6/7 helicase (2.5 M). These results suggest that heliquinomycin mainly targets actions of the replicative DNA helicases. Gel-retardation experiment indicates that heliquinomycin binds to single-stranded DNA. The single-stranded DNA-binding ability of MCM4/6/7 was affected in the presence of heliquinomycin. The data suggest that heliquinomycin inhibits the DNA helicase activity of MCM4/6/7 complex by stabilizing its interaction with single-stranded DNA. The Authors 2011. Published by Oxford University Press on behalf of the Japanese Biochemical Society.

AB - The antibiotic heliquinomycin inhibited cellular DNA replication at IC50 of 2.5 M without affecting level of chromatin-bound MCM4 and without activating the DNA replication stress checkpoint system, suggesting that heliquinomycin perturbs DNA replication mainly by inhibiting the activity of replicative DNA helicase that unwinds DNA duplex at replication forks. Among the DNA helicases involved in DNA replication, DNA helicase B was inhibited by heliquinomycin at IC50 of 4.3 M and RECQL4 helicase at IC50 of 14 M; these values are higher than that of MCM4/6/7 helicase (2.5 M). These results suggest that heliquinomycin mainly targets actions of the replicative DNA helicases. Gel-retardation experiment indicates that heliquinomycin binds to single-stranded DNA. The single-stranded DNA-binding ability of MCM4/6/7 was affected in the presence of heliquinomycin. The data suggest that heliquinomycin inhibits the DNA helicase activity of MCM4/6/7 complex by stabilizing its interaction with single-stranded DNA. The Authors 2011. Published by Oxford University Press on behalf of the Japanese Biochemical Society.

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