SCT1 mutants suppress the camptothecin sensitivity of yeast cells expressing wild-type DNA topoisomerase I.

Kauh EA; Bjornsti MA

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SCT1 mutants suppress the camptothecin sensitivity of yeast cells expressing wild-type DNA topoisomerase I.

机译：SCT1突变体抑制表达野生型DNA拓扑异构酶I的酵母细胞对喜树碱的敏感性。

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摘要

Camptothecin is a potent antineoplastic agent that interferes with the action of eukaryotic DNA topoisomerase I; the covalent enzyme-DNA intermediate is reversibly stabilized, leading to G2 arrest and cell death. We used a genetic screen to identify cellular factors, other than DNA topoisomerase I, that participate in the process of camptothecin-induced cell death. Following ethyl methanesulfonate mutagenesis of top1 delta yeast cells expressing plasmid-borne wild-type DNA topoisomerase I, six dominant suppressors of camptothecin toxicity were isolated that define a single genetic locus, sct1. Mutant SCT1 cells expressed DNA topoisomerase I protein of similar specific activity and camptothecin sensitivity to that of congenic, drug-sensitive sct1 cells, yet were resistant to camptothecin-mediated lethality. Moreover, camptothecin-treated SCT1 cells did not exhibit the G2-arrested, terminal phenotype characteristic of drug-treated wild-type cells. SCT1 cell sensitivity to other DNA-damaging agents suggests that alterations in SCT1 function suppress camptothecin-induced DNA damage produced in the presence of yeast DNA topoisomerase I.

机译：喜树碱是一种有效的抗肿瘤药，可干扰真核DNA拓扑异构酶I的作用。共价酶-DNA中间体可逆地稳定，导致G2阻滞和细胞死亡。我们使用遗传筛选来识别除喜树碱诱导的细胞死亡过程之外的其他细胞因子，而不是DNA拓扑异构酶I。在对表达质粒携带的野生型DNA拓扑异构酶I的top1三角酵母细胞进行甲磺酸乙酯诱变之后，分离了六个喜树碱毒性的主要抑制因子，这些抑制因子定义了一个遗传位点sct1。突变的SCT1细胞表达的DNA拓扑异构酶I蛋白具有与特异药物敏感性sct1细胞相似的比活性和喜树碱敏感性，但对喜树碱介导的致死性具有抗性。此外，喜树碱处理过的SCT1细胞没有表现出药物处理过的野生型细胞的G2阻滞，终末表型特征。 SCT1细胞对其他DNA破坏剂的敏感性表明，SCT1功能的改变可抑制在酵母DNA拓扑异构酶I存在下喜树碱诱导的DNA损伤。

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来源
《Proceedings of the National Academy of Sciences of the United States of America》 |1995年第14期|P.6299-6303|共5页
作者
Kauh EA; Bjornsti MA;
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作者单位

Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种 eng
中图分类自然科学总论;
关键词
Camptothecin; DNA Topoisomerases; Type I biosynthesis; DNA-Binding Proteins; 喜树碱; DNA结合蛋白质类; 真菌蛋白质类; 酵母菌; 酿酒; 转录因子;

机译：Camptothecin;DNA Topoisomerases;Type I biosynthesis;DNA-Binding Proteins;喜树碱;DNA结合蛋白质类;真菌蛋白质类;酵母菌;酿酒;转录因子;

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6. SCT1 mutants suppress the camptothecin sensitivity of yeast cells expressing wild-type DNA topoisomerase I. [O] . E A Kauh, M A Bjornsti 1995

机译：SCT1突变体抑制表达野生型DNA拓扑异构酶I的酵母细胞对喜树碱的敏感性。
7. SCT1 mutants suppress the camptothecin sensitivity of yeast cells expressing wild-type DNA topoisomerase I. [O] . Kauh, E A, Bjornsti, M A 1995

机译：SCT1突变体抑制表达野生型DNA拓扑异构酶I的酵母细胞对喜树碱的敏感性。
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SCT1 mutants suppress the camptothecin sensitivity of yeast cells expressing wild-type DNA topoisomerase I.

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