Mizushina Yoshiyuki, Xu Xianai, Asahara Hitomi, Takeuchi Ryo, Oshige Masahiko, Shimazaki Noriko, Takemura Masaharu, Yamaguchi Toyofumi, Kuroda Kazufumi, Linn Stuart, Yoshida Hiromi, Koiwai Osamu, Saneyoshi Mineo, Sugawara Fumio, Sakaguchi Kengo
Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan.
Biochem J. 2003 Feb 15;370(Pt 1):299-305. doi: 10.1042/BJ20021737.
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.
磺基喹喔啉二酰基甘油(SQDG)被报道为真核生物DNA聚合酶α和β的选择性抑制剂[Hanashima、Mizushina、Ohta、Yamazaki、Sugawara和Sakaguchi(2000年),《日本癌症研究杂志》91卷,第1073 - 1083页]以及一种免疫抑制剂[Matsumoto、Sahara、Fujita、Shimozawa、Takenouchi、Torigoe、Hanashima、Yamazaki、Takahashi、Sugawara等人(2002年),《移植》74卷,第261 - 267页]。本文的目的是更精确地阐明这种抑制作用的生化特性。正如预期的那样,SQDG在体外能够抑制哺乳动物DNA聚合酶的活性,如α、δ、η和κ,抑制浓度范围为2 - 5微摩尔,而对β和λ的抑制浓度范围为20 - 45微摩尔。然而,SQDG在浓度低于0.04微摩尔时仅能抑制哺乳动物DNA聚合酶ε(pol ε)的活性。与所测试的其他哺乳动物聚合酶相比,SQDG与哺乳动物pol ε的结合更紧密。此外,SQDG能够抑制鱼类和昆虫等动物的所有聚合酶的活性,但不能抑制植物和原核生物的聚合酶的活性。因此,SQDG应该被称为哺乳动物pol ε特异性抑制剂或动物聚合酶特异性抑制剂。据我们所知,这是关于哺乳动物pol ε特异性抑制剂的首次报道。