MECHANISM OF MUTAGENESIS BY O-6-METHYLGUANINE
MECHANISM OF MUTAGENESIS BY O-6-METHYLGUANINE
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DOI：
10.1038/308201a0
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发表时间：
1984-01-01
期刊：
影响因子：
64.8
通讯作者：
TOPAL, MD
中科院分区：
文献类型：
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作者：
EADIE, JS;CONRAD, M;TOPAL, MD
双链DNA的O 6-甲基鸟嘌呤（O 6 meG）损伤与突变1 - 3和肿瘤转化4，5有关。原则上，这些损伤至少可以通过三种不同的机制产生：双链DNA中G·C碱基对的直接烷基化6，7;与复制叉相关的DNA单链区域中鸟嘌呤残基的烷基化8，9; DNA前体池的烷基化10，随后在DNA复制过程中掺入O 6-甲基脱氧鸟苷三磷酸（O 6-medGTP）。所有三个事件之后的DNA生物合成将主要产生O 6-meG·T碱基对，因为O 6 meG优先与T11，12配对。我们在这里表明，O 6 meG·T碱基对是致突变的;烷基转移酶修复1，13，14在烷基化池核苷酸诱导的突变的产生中具有直接作用;大肠杆菌匹配修复系统15，16能够修复致突变的G·T中间体。
O6-methylguanine (O6meG) lesions of double-stranded DNA have been associated with mutation1–3and neoplastic transformation4,5. These lesions can, in principle, be produced by at least three different mechanisms: direct alkylation of G·C base pairs in double-stranded DNA6,7; alkylation of guanine residues in single-stranded regions of DNA associated with replication forks8,9; and alkylation of the DNA precursor pool10followed by incorporation ofO6-methyl deoxyguanosine triphosphate (O6-medGTP) during DNA replication. DNA biosynthesis subsequent to all three events will generate predominantly O6-meG·T base pairs as O6meG preferentially pairs with T11,12. We show here that O6meG·T base pairs are mutagenic; that transalkylase repair1,13,14has a direct role in the generation of mutations induced by alkylated pool nucleotides; and that theEscherichia colimismatch repair system15,16is capable of repairing mutagenic G·T intermediates.