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首页> 外文期刊>Biochemistry >Excision of products of oxidative DNA base damage by human NTH1 protein.
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Excision of products of oxidative DNA base damage by human NTH1 protein.

机译:排除人类NTH1蛋白对DNA的氧化作用。

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摘要

A functional human homologue of Escherichia coli endonuclease III (Nth-Eco protein) has recently been cloned and characterized [Aspinwall, R., Rothwell, D. G., Roldan-Arjona, T., Anselmino, C., Ward, C. J., Cheadle, J. P., Sampson, J. R., Lindahl, T., Harris, P. C., and Hickson, I. D. (1997) Proc. Natl. Acad. Sci. U.S.A., 94, 109-114]. This enzyme, designated hNTH1 protein, shares an extensive sequence similarity with Nth-Eco protein and a related enzyme from Schizosaccharomyces pombe (Nth-Spo protein). We investigated the substrate specificity of this human enzyme for oxidative DNA base damage, using the technique of gas chromatography/isotope-dilution mass spectrometry. Four different DNA substrates damaged by various free radical-generating systems were used. 5-Hydroxycytosine, thymine glycol, 5-hydroxy-6-hydrothymine, 5,6-dihydroxycytosine, and 5-hydroxyuracil were substrates of hNTH1 protein among 17 lesions found in DNA substrates. The substrate specificity and excision kinetics of the human enzyme were found to be significantly different from those of Nth-Spo and Nth-Eco proteins.
机译:大肠杆菌内切核酸酶III(Nth-Eco蛋白)的功能性人类同源物最近已被克隆和鉴定[Aspinwall,R.,Rothwell,DG,Roldan-Arjona,T.,Anselmino,C.,Ward,CJ,Cheadle,JP ,Sampson,JR,Lindahl,T.,Harris,PC和Hickson,ID(1997)Proc。 Natl。学院科学U.S.A.,94,109-114]。该酶称为hNTH1蛋白,与Nth-Eco蛋白和粟酒裂殖酵母的一种相关酶(Nth-Spo蛋白)具有广泛的序列相似性。我们使用气相色谱/同位素稀释质谱技术研究了这种人类酶对DNA氧化碱基损伤的底物特异性。使用了四种由各种自由基产生系统破坏的DNA底物。在DNA底物中发现的17种病变中,hNTH1蛋白的底物是5-羟基胞嘧啶,胸腺嘧啶乙二醇,5-羟基-6-氢胸腺嘧啶,5,6-二羟基胞嘧啶和5-羟基尿嘧啶。发现人类酶的底物特异性和切除动力学与Nth-Spo和Nth-Eco蛋白显着不同。

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