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NMR investigation of primer-template models: Structural effect of sequence downstream of a thymine template on mutagenesis in DNA replication

机译:底漆模板模型的NMR调查:DNA复制诱变胸腺嘧啶模板下游的结构效应

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Misaligned structures can occur in primer-templates during DNA replication, which can be bypassed and extended by low-fidelity polymerases and ultimately lead to mutations. In this study, we have investigated how the nucleotide downstream of a thymine template affects the primer-template structures upon misincorporation of dNTPs. The base pair structures at the replicating sites of a set of primer-template models containing either a G or an A downstream of the thymine template have been determined using NMR spectroscopy. Incorporation of dCTP and dTTP opposite 5'-GT and 5'-AT templates, respectively, can result in misaligned structures with a T-bulge. Depending on the downstream sequence, subsequent extension of the primers may stabilize the misaligned structures or cause the formation of mismatched structures. These results provide alternative pathways for base substitution and deletion errors during DNA replication by low-fidelity polymerases.
机译:在DNA复制期间可以在引物 - 模板中发生未对准的结构,其可以通过低保真聚合酶旁路和延伸,并最终导致突变。 在这项研究中,我们研究了胸腺嘧啶模板下游的核苷酸如何影响DNTPS的MIS掺入的引物模板结构。 使用NMR光谱法确定了含有G或胸腺嘧啶模板下游的一组引物模板模型的复制部位的碱基对结构。 DCTP和DTTP分别掺入5'-GT和5'-AT模板,可以导致具有T凸起的未对准结构。 根据下游序列,引物的后续延伸可以稳定错位的结构或导致形成不匹配的结构。 这些结果提供了低保性聚合酶在DNA复制期间基础取代和缺失误差的替代途径。

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