Structural Basis of the Mispairing of an Artificially Expanded Genetic Information System
Structural Basis of the Mispairing of an Artificially Expanded Genetic Information System
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DOI：
10.1016/j.chempr.2016.11.009
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发表时间：
2016-12-08
期刊：
影响因子：
23.5
通讯作者：
Burley, Glenn A.
中科院分区：
文献类型：
--
作者：
Reichenbach, Linus F.;Sobri, Ahmad Ahmad;Burley, Glenn A.
相对于天然存在的沃森-克里克碱基对，合成的核苷酸P通过独特的氢键排列与DNA双链体内的Z配对。通过PCR丢失这种合成的遗传信息导致P-Z转化为G-C碱基对。在这里，我们展示了结构和光谱证据，表明这种合成遗传信息的丢失是通过G-Z错配发生的。值得注意的是，G-Z错配对是塑性和pH依赖性的;它在pH 7.8时形成双氢键“滑动”对，当pH高于7.8时形成三氢键Z-G对。这项研究强调了需要强大的结构和功能方法来阐明下一代合成遗传碱基对发展中的突变机制。
Relative to naturally occurring Watson-Crick base pairs, the synthetic nucleotide P pairs with Z within DNA duplexes through a unique hydrogen-bond arrangement. The loss of this synthetic genetic information by PCR results in the conversion of P-Z into a G-C base pair. Here, we show structural and spectroscopic evidence that the loss of this synthetic genetic information occurs viaG-Z mispairing. Remarkably, the G-Z mispair is both plastic and pH dependent; it forms a double-hydrogen-bonded "slipped'' pair at pH 7.8 and a triple-hydrogen-bonded Z-G pair when the pH is above 7.8. This study highlights the need for robust structural and functional methods to elucidate the mechanisms of mutation in the development of next-generation synthetic genetic base pairs.