title: A sulphoquinovosyl diacylglycerol is a DNA polymerase epsilon inhibitor.
abstract: Sulphoquinovosyl diacylglycerol (SQDG) was reported as a selective inhibitor of eukaryotic DNA polymerases alpha and beta [Hanashima, Mizushina, Ohta, Yamazaki, Sugawara and Sakaguchi (2000) Jpn. J. Cancer Res. 91, 1073-1083] and an immunosuppressive agent [Matsumoto, Sahara, Fujita, Shimozawa, Takenouchi, Torigoe, Hanashima, Yamazaki, Takahashi, Sugawara et al. (2002) Transplantation 74, 261-267]. The purpose of this paper is to elucidate the biochemical properties of the inhibition more precisely. As expected, SQDG could inhibit the activities of mammalian DNA polymerases such as alpha, delta, eta and kappa in vitro in the range of 2-5 micro M, and beta and lambda in vitro in the range of 20-45 micro M. However, SQDG could inhibit only mammalian DNA polymerases epsilon (pol epsilon) activity at less than 0.04 micro M. SQDG bound more tightly to mammalian pol epsilon than the other mammalian polymerases tested. Moreover, SQDG could inhibit the activities of all the polymerases from animals such as fish and insect, but not of the polymerases from plant and prokaryotes. SQDG should, therefore, be called a mammalian pol epsilon-specific inhibitor or animal polymerase-specific inhibitor. To our knowledge, this represents the first report about an inhibitor specific to mammalian pol epsilon.
authors.affiliation: Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan. mizushin@nutr.kobegakuin.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mizushina
authors.forename: Xianai
authors.initials: X
authors.lastname: Xu
authors.forename: Hitomi
authors.initials: H
authors.lastname: Asahara
authors.forename: Ryo
authors.initials: R
authors.lastname: Takeuchi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Oshige
authors.forename: Noriko
authors.initials: N
authors.lastname: Shimazaki
authors.forename: Masaharu
authors.initials: M
authors.lastname: Takemura
authors.forename: Toyofumi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Kuroda
authors.forename: Stuart
authors.initials: S
authors.lastname: Linn
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Osamu
authors.initials: O
authors.lastname: Koiwai
authors.forename: Mineo
authors.initials: M
authors.lastname: Saneyoshi
authors.forename: Fumio
authors.initials: F
authors.lastname: Sugawara
authors.forename: Kengo
authors.initials: K
authors.lastname: Sakaguchi
mesh_terms: D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006017:Glycolipids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics
chemical_list: D004791:Enzyme Inhibitors; D006017:Glycolipids; C013694:sulfoquinovosyl diglyceride; D004257:DNA Polymerase II