Galactosyldiacylglycerol, a Mammalian DNA Polymerase α-Specific Inhibitor from a Sea Alga, Petalonia bingbamiae

Yoshiyuki MIZUSHINA; Yuichi SUGIYAMA; Hiromi YOSHIDA; Shinya HANASHIMA; Takayuki YAMAZAKI; Shinji KAMISUKI; Keisuke OHTA; Masaharu TAKEMURA; Toyofumi YAMAGUCHI; Akio MATSUKAGE; Shonen YOSHIDA; Mineo SANEYOSHI; Fumio SUGAWARA; Kengo SAKAGAUCHI

doi:10.1248/bpb.24.982

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Galactosyldiacylglycerol, a Mammalian DNA Polymerase α-Specific Inhibitor from a Sea Alga, Petalonia bingbamiae

Yoshiyuki MIZUSHINA, Yuichi SUGIYAMA, Hiromi YOSHIDA, Shinya HANASHIMA, Takayuki YAMAZAKI, Shinji KAMISUKI, Keisuke OHTA, Masaharu TAKEMURA, Toyofumi YAMAGUCHI, Akio MATSUKAGE, Shonen YOSHIDA, Mineo SANEYOSHI, Fumio SUGAWARA, Kengo SAKAGAUCHI

Author information

Yoshiyuki MIZUSHINA
Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, and High Technology Research Center, Kobe-Gakuin University
Yuichi SUGIYAMA
Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo
Hiromi YOSHIDA
Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, and High Technology Research Center, Kobe-Gakuin University
Shinya HANASHIMA
Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo
Takayuki YAMAZAKI
Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo
Shinji KAMISUKI
Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo
Keisuke OHTA
Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo
Masaharu TAKEMURA
Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine
Toyofumi YAMAGUCHI
Department of Biological Science, Teikyo University of Science and Technology
Akio MATSUKAGE
Department of Chemical and Biological Sciences, Japan Women’s University
Shonen YOSHIDA
Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine
Mineo SANEYOSHI
Department of Biological Science, Teikyo University of Science and Technology
Fumio SUGAWARA
Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo
Kengo SAKAGAUCHI
Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo

Keywords: DNA polymerase α, enzyme inhibitor, galactosyldiacylglycerol, sea alga, Petalonia bingbamiae

JOURNAL FREE ACCESS

2001 Volume 24 Issue 9 Pages 982-987

DOI https://doi.org/10.1248/bpb.24.982

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Abstract

The glycolipid galactosyldiacylglycerol (GDG), containing C16 : 0 and C18 : 1 fatty acids, was isolated from the sea alga Petalonia bingbamiae as a potent inhibitor of the activities of mammalian DNA polymerase α (pol. α). GDG, however, had no effect on pol. α from a fish or a higher plant. The inhibition of pol. α by GDG was dose-dependent with an IC₅₀ value of 54 μM. The compound did not influence the activities of other replicative DNA polymerases such as mammalian pol. δ, or repair-related enzymes such as mammalian pol. β. GDG also did not influence the activities of prokaryotic DNA polymerases such as the Klenow fragment of DNA polymerase I, T4 DNA polymerase, Taq DNA polymerase, DNA polymerases from the higher plant, cauliflower, or DNA metabolic enzymes such as calf thymus terminal deoxynucleotidyl transferase, human immunodeficiency virus type 1 reverse transcriptase and deoxyribonuclease I. Kinetic analysis of the compound showed that pol. α was non-competitively inhibited with respect to both the DNA template and the nucleotide substrate. In this study, we demonstrated the structure-function relationship in the selective inhibition of pol. α by the glycolipid group.

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