DNA strand specificity for UV-induced mutations in mammalian cells

DNA strand specificity for UV-induced mutations in mammalian cells
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哺乳动物细胞中紫外线诱导突变的 DNA 链特异性

DOI:
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发表时间:
1989
影响因子:
5.3
通讯作者:
A. V. van Zeeland
A. V. van Zeeland
中科院分区:
生物学2区
文献类型:
--
作者:
H. Vrieling;M. V. van Rooijen;N A Groen;M. Z. Zdzienicka;J. Simons;P H Lohman;A. V. van Zeeland

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在来自UV敏感的中国仓鼠细胞(V-H1)和亲本系(V79)的UV诱导的hprt突变体中研究了DNA修复对UV光(254 nm)诱导的突变的分子性质的影响。通过体外扩增hprt cDNA的序列分析,确定了V79的19个hprt突变体和V-H1细胞的17个hprt突变体的hprt外显子序列中点突变的性质。在V79细胞中的突变谱包括单和串联双碱基对的变化,而在V-H1细胞中也检测到三个移码突变。所有V-H1突变体的碱基对变化是由于GC-AT转换。相比之下,在V79中,除了GC-CG颠换之外,所有可能的碱基对变化类型都存在。在这组中,70%的突变是颠换。由于除了一个突变外,所有突变都发生在二嘧啶位点,因此假设它们是由这些位点的UV诱导的光产物引起的。在V79细胞中,17个碱基对的变化中有11个是由hprt基因非转录链中的光产物引起的。然而,在V-H1细胞中,这是完全缺乏从hprt基因的嘧啶二聚体的去除,并显示出紫外线诱导的突变频率增强7倍,11个碱基对的变化中的10个是由在转录链的hprt基因的光产物引起的。我们推测,这种极端的链特异性在V-H1细胞是由于在DNA复制的领先和滞后链的保真度的差异。此外,我们提出,在正常的V79细胞中,两个过程确定的链特异性的UV诱导的突变的hprt基因,即优先修复的转录链的hprt基因和更高的保真度的DNA复制的非转录链相比,转录链。
The influence of DNA repair on the molecular nature of mutations induced by UV light (254 nm) was investigated in UV-induced hprt mutants from UV-sensitive Chinese hamster cells (V-H1) and the parental line (V79). The nature of point mutations in hprt exon sequences was determined for 19 hprt mutants of V79 and for 17 hprt mutants of V-H1 cells by sequence analysis of in vitro-amplified hprt cDNA. The mutation spectrum in V79 cells consisted of single- and tandem double-base pair changes, while in V-H1 cells three frameshift mutations were also detected. All base pair changes in V-H1 mutants were due to GC----AT transitions. In contrast, in V79 all possible classes of base pair changes except the GC----CG transversion were present. In this group, 70% of the mutations were transversions. Since all mutations except one did occur at dipyrimidine sites, the assumption was made that they were caused by UV-induced photoproducts at these sites. In V79 cells, 11 out of 17 base pair changes were caused by photoproducts in the nontranscribed strand of the hprt gene. However, in V-H1 cells, which are completely deficient in the removal of pyrimidine dimers from the hprt gene and which show a UV-induced mutation frequency enhanced seven times, 10 out of 11 base pair changes were caused by photoproducts in the transcribed strand of the hprt gene. We hypothesize that this extreme strand specificity in V-H1 cells is due to differences in fidelity of DNA replication of the leading and the lagging strand. Furthermore, we propose that in normal V79 cells two processes determine the strand specificity of UV-induced mutations in the hprt gene, namely preferential repair of the transcribed strand of the hprt gene and a higher fidelity of DNA replication of the nontranscribed strand compared with the transcribed strand.
DOI: 10.1073/pnas.78.6.3388
发表时间: 1981-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
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DOI: --
发表时间: 1982
期刊: Radiation research
影响因子: 3.4
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DOI: --
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影响因子: --
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