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甲氨蝶呤抗性利什曼原虫中的不稳定DNA扩增由染色体外环状结构组成,这些环状结构在稳定过程中重新定位。

Unstable DNA amplifications in methotrexate-resistant Leishmania consist of extrachromosomal circles which relocalize during stabilization.

作者信息

Beverley S M, Coderre J A, Santi D V, Schimke R T

出版信息

Cell. 1984 Sep;38(2):431-9. doi: 10.1016/0092-8674(84)90498-7.

DOI:10.1016/0092-8674(84)90498-7
PMID:6467372
Abstract

Methotrexate-resistant Leishmania tropica contain two separate regions of DNA amplification, one encoding the bifunctional thymidylate synthetase-dihydrofolate reductase (TS-DHFR) characteristic of protozoans and the other of yet unknown function. The amplified DNAs are initially found as extrachromosomal closed circular forms, which are unstable in the absence of selection. After prolonged culture in methotrexate the amplified DNAs are found as repetitive arrays associated with the chromosomal DNA fraction after CsCl-ethidium bromide density gradient centrifugation, and are stable once selection is removed. The molecular description of gene amplification in Leishmania thus closely parallels the cytological features of gene amplification in cultured mammalian cells.

摘要

对甲氨蝶呤耐药的热带利什曼原虫含有两个独立的DNA扩增区域,一个编码原生动物特有的双功能胸苷酸合成酶-二氢叶酸还原酶(TS-DHFR),另一个功能未知。扩增的DNA最初以染色体外闭合环状形式存在,在无选择条件下不稳定。在甲氨蝶呤中长时间培养后,经氯化铯-溴化乙锭密度梯度离心,扩增的DNA以与染色体DNA部分相关的重复阵列形式存在,去除选择后则稳定。因此,利什曼原虫基因扩增的分子描述与培养的哺乳动物细胞中基因扩增的细胞学特征极为相似。

相似文献

1
Unstable DNA amplifications in methotrexate-resistant Leishmania consist of extrachromosomal circles which relocalize during stabilization.甲氨蝶呤抗性利什曼原虫中的不稳定DNA扩增由染色体外环状结构组成,这些环状结构在稳定过程中重新定位。
Cell. 1984 Sep;38(2):431-9. doi: 10.1016/0092-8674(84)90498-7.
2
Overproduction of a bifunctional thymidylate synthetase-dihydrofolate reductase and DNA amplification in methotrexate-resistant Leishmania tropica.
Proc Natl Acad Sci U S A. 1983 Apr;80(8):2132-6. doi: 10.1073/pnas.80.8.2132.
3
Role of the locus and of the resistance gene on gene amplification frequency in methotrexate resistant Leishmania tarentolae.位点及抗性基因对甲氨蝶呤抗性利什曼原虫基因扩增频率的作用
Nucleic Acids Res. 1999 Sep 15;27(18):3653-9. doi: 10.1093/nar/27.18.3653.
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DNA amplification in antifolate-resistant Leishmania. The thymidylate synthase-dihydrofolate reductase gene and abundant mRNAs.
J Biol Chem. 1985 Jul 5;260(13):7809-12.
5
Transcriptional mapping of the amplified region encoding the dihydrofolate reductase-thymidylate synthase of Leishmania major reveals a high density of transcripts, including overlapping and antisense RNAs.硕大利什曼原虫二氢叶酸还原酶-胸苷酸合成酶编码扩增区域的转录图谱显示转录本密度很高,包括重叠RNA和反义RNA。
Mol Cell Biol. 1989 Sep;9(9):3959-72. doi: 10.1128/mcb.9.9.3959-3972.1989.
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Leishmania gene amplification: a mechanism of drug resistance.利什曼原虫基因扩增:一种耐药机制。
Ann Trop Med Parasitol. 1994 Apr;88(2):123-30. doi: 10.1080/00034983.1994.11812849.
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Primary structure of the gene encoding the bifunctional dihydrofolate reductase-thymidylate synthase of Leishmania major.硕大利什曼原虫双功能二氢叶酸还原酶-胸苷酸合成酶编码基因的一级结构
Proc Natl Acad Sci U S A. 1986 Apr;83(8):2584-8. doi: 10.1073/pnas.83.8.2584.
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H DNA amplification in Leishmania resistant to both arsenite and methotrexate.对亚砷酸盐和甲氨蝶呤均耐药的利什曼原虫中的H DNA扩增。
Mol Biochem Parasitol. 1989 May 1;34(2):189-91. doi: 10.1016/0166-6851(89)90010-8.
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Electron microscopy of amplified DNA forms in antifolate-resistant Leishmania.
J Biol Chem. 1987 Oct 25;262(30):14618-24.
10
Amplified DNAs in laboratory stocks of Leishmania tarentolae: extrachromosomal circles structurally and functionally similar to the inverted-H-region amplification of methotrexate-resistant Leishmania major.实验室保藏的热带利什曼原虫中的扩增DNA:染色体外环状结构,在结构和功能上与耐甲氨蝶呤的硕大利什曼原虫的倒H区扩增相似。
Mol Cell Biol. 1988 Dec;8(12):5188-99. doi: 10.1128/mcb.8.12.5188-5199.1988.

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