Tripathi Shailesh, Paukstelis Paul J
Department of Chemistry & Biochemistry, University of Maryland, 8051 Reagents Drive, College Park, MD, 20742, USA.
National Institute of Mental Health and Neurosciences, Hosur Road 560029, Bengaluru, India.
Chembiochem. 2016 Jun 16;17(12):1177-83. doi: 10.1002/cbic.201500491. Epub 2016 Jan 5.
DNA can adopt many other structures beyond the canonical B-form double helix. These alternative DNA structures have become increasingly significant as new biological roles are found for them. Additionally, there has been a growing interest in using non-canonical base pairs to provide structural diversity for designing DNA architectures for nanotechnology applications. We recently described the crystal structure of d(ACTCGGATGAT), which forms a tetraplex through parallel-stranded homo-base pairs and nucleobase intercalation. The homoduplex region contains a d(YGA⋅YGA) motif observed in crystal and solution structures. Here, we examine the structural implications of the homopyrimidine base pair within this motif. We determined crystal structures of two variants that differ from the original structure in the homopyrimidine base pairs and number of d(YGA) motifs. Our results show that the intercalation-locked tetraplex motif is predictable in these different sequence contexts and that substituting C⋅C base pairs for T⋅T base pairs introduces asymmetry to the homoduplex. These results have important implications for utilizing d(YGA) motifs in DNA crystal design and could provide a basis for understanding how local structures could be associated with repeat expansions.
除了经典的B型双螺旋结构外，DNA还可以呈现许多其他结构。随着人们发现这些替代DNA结构具有新的生物学作用，它们的重要性日益凸显。此外，利用非经典碱基对为纳米技术应用设计DNA结构提供结构多样性的兴趣也在不断增加。我们最近描述了d(ACTCGGATGAT)的晶体结构，它通过平行链同碱基对和核碱基插入形成四链体。同源双链区域包含在晶体和溶液结构中观察到的d(YGA⋅YGA)基序。在这里，我们研究了该基序内同嘧啶碱基对的结构影响。我们确定了两个变体的晶体结构，它们在同嘧啶碱基对和d(YGA)基序数量上与原始结构不同。我们的结果表明，在这些不同的序列背景下，插入锁定四链体基序是可预测的，并且用C⋅C碱基对替代T⋅T碱基对会给同源双链引入不对称性。这些结果对于在DNA晶体设计中利用d(YGA)基序具有重要意义，并可能为理解局部结构如何与重复序列扩增相关联提供基础。
