Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
J Phys Chem B. 2012 Feb 16;116(6):1999-2007. doi: 10.1021/jp211666k. Epub 2012 Feb 3.
Strand slippage has been found to occur in primer-templates containing a templating thymine, cytosine, and guanine, leading to the formation of misaligned structures with a single-nucleotide bulge. If remained in the active site of low-fidelity polymerases during DNA replication, these misaligned structures can ultimately bring about deletion mutations. In this study, we performed NMR investigations on primer-template models containing a templating adenine. Similar to our previous results on guanine, adenine templates are also less prone to strand slippage than pyrimidine templates. Misalignment occurs only in primer-templates that form a terminal C·G or G·C base pair. Together with our previous findings on thymine, cytosine, and guanine templates, the present study reveals strand slippage can occur in any kind of natural templating bases during DNA replication, providing insights into the origin of mutation hotspots in natural DNA sequences. In addition to the type of incoming base upon misincorporation, the propensity of strand slippage in primer-templates depends also on the type of templating base, its upstream and downstream bases.
链滑动已被发现发生在含有模板胸腺嘧啶、胞嘧啶和鸟嘌呤的引物-模板中，导致形成具有单个核苷酸凸起的不对齐结构。如果在 DNA 复制过程中留在低保真度聚合酶的活性位点中，这些不对齐结构最终可能导致缺失突变。在这项研究中，我们对含有模板腺嘌呤的引物-模板模型进行了 NMR 研究。与我们之前关于鸟嘌呤的结果类似，腺嘌呤模板比嘧啶模板更不容易发生链滑动。只有形成末端 C·G 或 G·C 碱基对的引物-模板才会发生不对齐。结合我们之前关于胸腺嘧啶、胞嘧啶和鸟嘌呤模板的发现，本研究揭示了链滑动在 DNA 复制过程中可能发生在任何类型的天然模板碱基中，为自然 DNA 序列中突变热点的起源提供了线索。除了错误掺入时引入碱基的类型外，引物-模板中链滑动的倾向还取决于模板碱基的类型、其上下游碱基。
