MISMATCH CORRECTION AT O-6-METHYLGUANINE RESIDUES IN ESCHERICHIA-COLI DNA
MISMATCH CORRECTION AT O-6-METHYLGUANINE RESIDUES IN ESCHERICHIA-COLI DNA
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DOI：
10.1038/296868a0
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发表时间：
1982-01-01
期刊：
影响因子：
64.8
通讯作者：
MARINUS, MG
中科院分区：
文献类型：
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作者：
KARRAN, P;MARINUS, MG
大肠杆菌有一个校正系统，可以去除 DNA1 中不匹配的碱基。缺乏主要 DNA 腺嘌呤甲基化酶 2 的突变体 (dam) 对碱基类似物诱变剂（如 2-氨基嘌呤 3）的作用高度敏感，并且似乎在错配校正方面存在缺陷。对碱基类似物抗性的突变体的表型回复体包括mutLormutSgenes4中的第二个位点突变，这也是校正系统的一部分。我们在此报告E。大肠杆菌 dammutants 对 DNA 甲基化剂 N-甲基-N'-硝基-N-亚硝基胍 (MNNG) 也敏感，它将 O6-甲基鸟嘌呤 (m6G) 引入 DNA。然而，使用仅产生少量这种烷基化碱的甲基化剂并没有观察到这种敏感性。此外，将 amutL 或 amutSmutation 引入大坝菌株中消除了对 MNNG 的敏感性。这些结果表明错配校正发生在 DNA 中的 m6G 残基处。这些损伤在 DNA 聚合酶 I 介导的体外 DNA 合成中发生错误编码，并且已知在体内具有诱变性 6。然而，DNA 中 m6G 残基的错配校正似乎不会导致 MNNG 诱导突变的减少。
Escherichia colihas a correction system which removes mismatched bases from DNA1. Mutants (dam) which lack the major DNA adenine methylase2are hypersensitive to the effects of base analogue mutagens such as 2-aminopurine3and appear to be defective in mismatch correction. Phenotypic revertants ofdammutants to base analogue resistance include second site mutations inmutLormutSgenes4, which are also part of the correction system. We report here thatE. coli dammutants are also sensitive to the DNA methylating agentN-methyl-N′-nitro-N-nitrosoguanidine (MNNG), which introducesO6-methylguanine (m6G) into the DNA. This sensitivity, however, was not observed using methylating agents which generate only low amounts of this alkylated base. Furthermore, the introduction of either amutLor amutSmutation intodamstrains abolished the sensitivity to MNNG. These results suggest that mismatch correction occurs at m6G residues in DNA. These lesions miscode in DNA polymerase I-mediated DNA synthesisin vitro5and are known to be mutagenicin vivo6. Nevertheless, it appears that mismatch correction at m6G residues in DNA does not lead to reduced induction of mutation by MNNG.