Genome integrity is constantly challenged by endogenous or exogenous genotoxic agents, which can give rise to various DNA adducts. After metabolic activation, tobacco-specific nitrosamines N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) can lead to pyridyloxobutylphosphotriesters (POB-PTEs) in DNA. Here, we synthesized oligodeoxyribonucleotides containing a site-specifically inserted SP- or RP-POB-PTE flanked by two thymidines, and we examined the impact that these lesions have on DNA replication in Escherichia coli cells. We found that these two lesions are not strong impediments to DNA replication, and their replicative bypass is not modulated by genetic depletion of the three SOS-induced DNA polymerases or Ada protein. In addition, neither SP- nor RP-POB-PTEs was mutagenic in E. coli cells. Together, our study unveiled, for the first time, the influence of tobacco-specific nitrosamine-induced POB-PTE lesions on DNA replication in vivo.

中文翻译：

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吡啶基氧丁基磷酸三酯病变在细胞中的复制。

基因组完整性不断受到内源性或外源性遗传毒性剂的挑战，这些毒性剂会引起各种DNA加合物的产生。代谢激活后，烟草特有的亚硝胺N'-亚硝基亚硝基烟碱（NNN）和4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）可以导致DNA中的吡啶基氧丁基磷酸三酯（POB-PTE）。在这里，我们合成了寡聚脱氧核糖核苷酸，其中包含一个位点特异性插入的SP-或RP-POB-PTE，两侧是两个胸苷，我们研究了这些损伤对大肠杆菌细胞中DNA复制的影响。我们发现这两个病变不是DNA复制的强大障碍，并且它们的复制旁路不受三种SOS诱导的DNA聚合酶或Ada蛋白的遗传消耗的调节。另外，SP-和RP-POB-PTE在大肠杆菌细胞中均不致突变。一起，