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金属硫蛋白基因中的DNA修复随转录激活而增加。

DNA repair in the metallothionein gene increases with transcriptional activation.

作者信息

Okumoto D S, Bohr V A

机构信息

Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892.

出版信息

Nucleic Acids Res. 1987 Dec 10;15(23):10021-30. doi: 10.1093/nar/15.23.10021.

DOI:10.1093/nar/15.23.10021
PMID:2827103
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC306548/
Abstract

We have studied DNA repair in the Chinese Hamster Ovary (CHO) metallothionein (MT) gene after UV-light induced damage. The repair was examined comparatively with or without transcriptional activation of the gene by incubation in the presence of the heavy metal ZnCl2. Whereas the repair efficiency was very low in the uninduced state, it increased significantly after induction of the gene. The presence of ZnCl2 did not appear to change other repair parameters in the cells. The overall genome DNA repair efficiency after UV irradiation was similar whether or not the gene was induced and the preferential DNA repair pattern in the essential dihydrofolate reductase (DHFR) gene which we have previously described was unaffected by the presence of ZnCl2. Based upon repair analysis in two different restriction fragments containing the MT I gene, we conclude that the region of efficient repair after induction is considerably larger than the 1 kb size of the gene. The results suggest that the accessibility of a genomic region to DNA repair enzymes may be regulated by the local chromatin structure in a dynamic manner.

摘要

我们研究了紫外线诱导损伤后中国仓鼠卵巢(CHO)金属硫蛋白(MT)基因的DNA修复情况。通过在重金属ZnCl₂存在下孵育,比较了该基因转录激活或未激活时的修复情况。在未诱导状态下,修复效率非常低,但基因诱导后显著提高。ZnCl₂的存在似乎并未改变细胞中的其他修复参数。无论该基因是否被诱导,紫外线照射后整个基因组DNA的修复效率相似,并且我们之前描述的必需二氢叶酸还原酶(DHFR)基因中的优先DNA修复模式不受ZnCl₂存在的影响。基于对包含MT I基因的两个不同限制片段的修复分析,我们得出结论,诱导后有效修复的区域比该基因1 kb的大小要大得多。结果表明,基因组区域对DNA修复酶的可及性可能受到局部染色质结构的动态调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb64/306548/c43e17ca2409/nar00267-0399-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb64/306548/c43e17ca2409/nar00267-0399-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb64/306548/c43e17ca2409/nar00267-0399-a.jpg

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本文引用的文献

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cDNA cloning and nucleotide sequence comparison of Chinese hamster metallothionein I and II mRNAs.中国仓鼠金属硫蛋白I和II mRNA的cDNA克隆及核苷酸序列比较
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Transcriptionally active chromatin.转录活性染色质
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Demethylation enhances removal of pyrimidine dimers from the overall genome and from specific DNA sequences in Chinese hamster ovary cells.去甲基化增强了中国仓鼠卵巢细胞中整个基因组以及特定DNA序列上嘧啶二聚体的去除。
Mol Cell Biol. 1989 Apr;9(4):1594-603. doi: 10.1128/mcb.9.4.1594-1603.1989.
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DNA repair at the level of the gene: molecular and clinical considerations.基因水平的DNA修复:分子及临床考量
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DNA repair in the c-myc proto-oncogene locus: possible involvement in susceptibility or resistance to plasmacytoma induction in BALB/c mice.c-myc原癌基因位点的DNA修复:可能与BALB/c小鼠浆细胞瘤诱导的易感性或抗性有关。
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Xeroderma pigmentosum complementation group C cells remove pyrimidine dimers selectively from the transcribed strand of active genes.着色性干皮病C互补组细胞从活性基因的转录链中选择性地去除嘧啶二聚体。
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DNA repair in an active gene: removal of pyrimidine dimers from the DHFR gene of CHO cells is much more efficient than in the genome overall.活跃基因中的DNA修复:从CHO细胞的二氢叶酸还原酶(DHFR)基因中去除嘧啶二聚体比在整个基因组中更有效。
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Coordinate expression of amplified metallothionein I and II genes in cadmium-resistant Chinese hamster cells.金属硫蛋白I和II基因在镉抗性中国仓鼠细胞中的协同表达。
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Cell. 1986 May 9;45(3):417-23. doi: 10.1016/0092-8674(86)90327-2.
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Metallothionein.金属硫蛋白
Annu Rev Biochem. 1986;55:913-51. doi: 10.1146/annurev.bi.55.070186.004405.
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Preferential DNA repair of an active gene in human cells.人类细胞中活性基因的优先DNA修复。
Proc Natl Acad Sci U S A. 1986 Dec;83(23):8878-82. doi: 10.1073/pnas.83.23.8878.
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Survival of UV-irradiated mammalian cells correlates with efficient DNA repair in an essential gene.紫外线照射的哺乳动物细胞的存活与一个必需基因中的高效DNA修复相关。
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Characterization of a DNA repair domain containing the dihydrofolate reductase gene in Chinese hamster ovary cells.中国仓鼠卵巢细胞中含二氢叶酸还原酶基因的DNA修复结构域的表征
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