INVIVO MUTAGENESIS BY O-6-METHYLGUANINE BUILT INTO A UNIQUE SITE IN A VIRAL GENOME
INVIVO MUTAGENESIS BY O-6-METHYLGUANINE BUILT INTO A UNIQUE SITE IN A VIRAL GENOME
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DOI：
10.1073/pnas.81.20.6271
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发表时间：
1984-01-01
期刊：
影响因子：
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通讯作者：
ESSIGMANN, JM
中科院分区：
文献类型：
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作者：
LOECHLER, EL;GREEN, CL;ESSIGMANN, JM
用单链M13mp8基因组研究了化学致癌物-DNA加合物O6MeGua(O6MeGua)的致突变性。用该载体转化大肠杆菌MM294A细胞获得了后代噬菌体，其中0.4%的噬菌体在其PstI位点发生突变。在另一项实验中，细胞中的O6MeGua-DNA甲基转移酶(amN O6MeGua-修复蛋白)水平在病毒DNA摄取之前被N-甲基-N‘-硝基-N-亚硝基-N-亚硝胺(MNNG)处理。在这些细胞中，O6MeGua的突变频率随着MNNG剂量的增加而增加(最高突变频率为20%)。对60个突变基因组的DNA序列分析表明，O6MeGua只诱导G-A转换。
The mutagenicity of O6-methylguanine (O6MeGua), a chemical carcinogen-DNA adduct, was studied in vivo by using a single-stranded M13mp8 genome in which a single O6MeGua residue was positioned in the unique recognition site for the restriction endonuclease PstI. Transformation of Escherichia coli MM294A cells with this vector gave progeny phage, of which 0.4% were mutated in their PstI site. In a separate experiment, cellular levels of O6MeGua-DNA methyltransferase (amn O6MeGua-repair protein) were depleted by treatment with N-methyl-N''-nitro-N-nitrosoguanidine (MNNG) prior to viral DNA uptake. In these cells, the mutation frequency due to O6MeGua increased with increasing MNNG dose (the highest mutation frequency observed was 20%). DNA sequence analysis of 60 mutant genomes revealed that O6MeGua induced exclusively G-to-A transitions.