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嵌入药物对动物细胞线粒体DNA聚合酶γ的抑制作用。

The inhibition of mitochondrial DNA polymerase gamma from animal cells by intercalating drugs.

作者信息

Tarrago-Litvak L, Viratelle O, Darriet D, Dalibart R, Graves P V, Litvak S

出版信息

Nucleic Acids Res. 1978 Jun;5(6):2197-210. doi: 10.1093/nar/5.6.2197.

DOI:10.1093/nar/5.6.2197
PMID:673850
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC342153/
Abstract

DNA polymerase gamma from purified nuclei of EMT-6 cells (mice) seems to be identical to the mitochondrial DNA polymerase from the same source following several criteria. These two enzyme activities are strongly inhibited by ethidium bromide and acriflavin, while proflavin, acridine orange, daunomycin and chloroquine inhibition is less pronounced. In the case of DNA polymerases alpha and beta very little inhibition by ethidium bromide was observed. Intercalation of this dye in a poly dA-dT 12-18 template-primer was studied spectrophotometrically under conditions similar to those in the in vitro DNA polymerase assay. The polymerase assay. The inhibition by this drug of the mitochondrial DNA polymerase gamma activity was shown to be competitive at varying concentrations of TTP while the inhibition was of the non-competitive type at different concentrations of poly dA-dT 12-18. We conclude that the drug, most probably in the intercalated form, is able to interact with the active site (s) of mitochondrial DNA polymerase.

摘要

来自EMT - 6细胞(小鼠)纯化细胞核的DNA聚合酶γ,根据多项标准,似乎与来自同一来源的线粒体DNA聚合酶相同。这两种酶活性受到溴化乙锭和吖啶黄素的强烈抑制,而原黄素、吖啶橙、柔红霉素和氯喹的抑制作用则不太明显。对于DNA聚合酶α和β,观察到溴化乙锭的抑制作用很小。在类似于体外DNA聚合酶测定的条件下,用分光光度法研究了这种染料在聚dA - dT 12 - 18模板 - 引物中的嵌入情况。在不同浓度的TTP下,该药物对线粒体DNA聚合酶γ活性的抑制作用表现为竞争性,而在不同浓度的聚dA - dT 12 - 18下,抑制作用为非竞争性类型。我们得出结论,该药物很可能以嵌入形式能够与线粒体DNA聚合酶的活性位点相互作用。

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本文引用的文献

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Protein measurement with the Folin phenol reagent.使用福林酚试剂进行蛋白质测定。
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Enzymatic synthesis of deoxyribonucleic acid. IX. The polymerase formed after T2 bacteriophage infection of Escherichia coli: a new enzyme.脱氧核糖核酸的酶促合成。IX. T2噬菌体感染大肠杆菌后形成的聚合酶:一种新酶。
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Characteristics of a serially transplanted mouse mammary tumor and its tissue-culture-adapted derivative.连续移植的小鼠乳腺肿瘤及其适应组织培养的衍生物的特征。
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Graphical analyses on binding of ligands to a two-sited system. Theoretical treatments exemplified on yeast phosphoglycerate kinase.配体与双位点系统结合的图形分析。以酵母磷酸甘油酸激酶为例的理论处理。
Arch Biochem Biophys. 1973 Oct;158(2):754-62. doi: 10.1016/0003-9861(73)90570-5.
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A DNA-directed DNA polymerase from murine liver mitochondria.来自小鼠肝脏线粒体的一种DNA指导的DNA聚合酶。
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10
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