The induction of errors during in vitro DNA synthesis following chloroacetaldehyde-treatment of poly(dA-dT) and poly(dC-dG) templates.

The induction of errors during in vitro DNA synthesis following chloroacetaldehyde-treatment of poly(dA-dT) and poly(dC-dG) templates.
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氯乙醛处理聚(dA-dT)和聚(dC-dG)模板后体外 DNA 合成过程中错误的诱导。

DOI:
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发表时间:
1981
期刊:
影响因子:
4.7
通讯作者:
D. Hathway
D. Hathway
中科院分区:
医学2区
文献类型:
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作者:
J. Hall;R. Saffhill;T. Green;D. Hathway

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氯乙醛是人类致癌物氯乙烯的重排代谢产物,与DNA样聚合物聚(dA-dT)和聚(dC-dG)反应,形成腺嘌呤和胞嘧啶碱基的乙烯基加合物。这些处理过的聚合物,当用作E. coli DNA聚合酶I在体外测定中显示出指导DNA合成的能力降低。同时,掺入了增加的非互补核苷酸的相对水平。对于聚(dA-dT)模板,每存在约60个乙烯腺嘌呤残基,就掺入1个dGMP残基,同时未检测到dCMP的错误掺入增加。使用聚(dC-dG)模板,dAMP或dTMP的1个错误掺入分别在约30和80个乙烯胞嘧啶残基的存在下发生。最近邻分析显示,使用修饰的聚(dC-dG)模板,大部分错误被掺入相反的胞嘧啶(或修饰的胞嘧啶)碱基。
Chloroacetaldehyde, a rearranged metabolic product of the human carcinogen vinyl chloride, reacts with the DNA-like polymers poly(dA-dT) and poly(dC-dG) to form etheno-adducts of the adenine and cytosine bases. These treated polymers, when used as templates for E. coli DNA polymerase I in an in vitro assay, show a decreased ability to direct DNA synthesis. At the same time, increased relative levels of non-complementary nucleotides are incorporated. With the poly(dA-dT) templates 1 dGMP residue is incorporated for every approx 60 ethenoadenine residues present whilst no increased misincorporation of dCMP was detected. With the poly(dC-dG) templates 1 misincorporation of dAMP or dTMP occurred in the presence of approx 30 and 80 ethenocytosine residues respectively. A nearest neighbour analysis shows that with the modified poly(dC-dG) templates the majority of the errors were incorporated opposite cytosine (or modified cytosine) bases.