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以甲基化聚(dA-dT)模板进行DNA合成:O4-甲基胸腺嘧啶作为促诱变碱基的可能作用。

DNA-synthesis with methylated poly(dA-dT) templates: possible role of O4-methylthymine as a pro-mutagenic base.

作者信息

Abbott P J, Saffhill R

出版信息

Nucleic Acids Res. 1977 Mar;4(3):761-9. doi: 10.1093/nar/4.3.761.

Abstract

The alternating copolymer poly(dA-dT) has been methylated with either dimethyl sulphate (DMS) or N-methyl-N-nitrosourea (MNU) and the levels of the various methylation products determined. In addition to the methylated adenines formed by both methylating agents, MNU resulted also in the formation of 3-methylthymine, O4-methylthymine and phosphotriesters. The methylated polymers have been ution of complementary and non-complementary nucleotides determined. With the DMS methylated template no wrong nucleotide incorporation was detectable, but with the MNU methylated polymer the incorporation of dGMP was observed. The amount of dGMP incorporated correlated with the level of O4-methylthymine in the template over the range of methylation studied. The results indicate that O4-methylthymine is capable of miscoding on a one-to-one basis while the products of DMS methylation (1-, 3- and 7-methyladenines), and also possibly the phosphotriesters, do not lead to any misincorporation.

摘要

交替共聚物聚(dA-dT)已用硫酸二甲酯(DMS)或N-甲基-N-亚硝基脲(MNU)进行甲基化,并测定了各种甲基化产物的水平。除了两种甲基化剂形成的甲基化腺嘌呤外,MNU还导致了3-甲基胸腺嘧啶、O4-甲基胸腺嘧啶和磷酸三酯的形成。已测定了甲基化聚合物中互补和非互补核苷酸的情况。用DMS甲基化的模板未检测到错误核苷酸掺入,但用MNU甲基化的聚合物观察到了dGMP的掺入。在所研究的甲基化范围内,掺入的dGMP量与模板中O4-甲基胸腺嘧啶的水平相关。结果表明,O4-甲基胸腺嘧啶能够一对一地错编码,而DMS甲基化产物(1-、3-和7-甲基腺嘌呤)以及可能的磷酸三酯不会导致任何错误掺入。

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