Bansal Aparna, Phogat Priyanka, Kukreti Shrikant
Nucleic Acids Research Lab, Department of Chemistry, University of Delhi (North Campus), Delhi, 110007, India.
Department of Chemistry, Hansraj College, University of Delhi, Delhi, 110007, India.
Biochem Biophys Rep. 2025 Aug 18;43:102203. doi: 10.1016/j.bbrep.2025.102203. eCollection 2025 Sep.
DNA is polymorphic, as with four nucleobases, it can be configured in a number of secondary structures. The four-stranded DNA structures consisting of G-tetrads have especially been intriguing because of their proven existence in human cells. Due to the high prevalence of putative G-quadruplex-forming sequence motifs in the human genome, scientists in recent years have highlighted the potential of exploiting these exotic structures for targeted therapies for various cancers. G-quadruplexes are the most common and well-studied arrangements of four guanines; however, other possible non-canonical arrangements of nucleobases have also been reported. Herein, using Gel electrophoresis, Circular Dichroism, UV & CD-thermal denaturation methods, and NMR, we suggested that a double repeat of telomere (TAG) shows a structural switch from a non-canonical intramolecular triplex to a non-conventional tetrad other than an antiparallel G-quadruplex. This transition is mediated by increasing Na cation concentration from 0.1 M to 1.0 M, and the tetrad is fairly stabilised by a hydrogen-bonded cyclic array of non-canonical/mismatch base pairs (G∗G, G∗T, and T∗T). Intriguingly, such a structural transition was not manifested in the presence of K ions. To the best of our knowledge, such a cation-specific non-canonical structural switch, in a telomeric sequence, has not been proposed to date.
DNA具有多态性，由于其含有四种核碱基，所以能够形成多种二级结构。由G-四联体组成的四链DNA结构尤其引人关注，因为它们已在人类细胞中被证实存在。由于人类基因组中潜在的G-四链体形成序列基序普遍存在，近年来科学家们强调了利用这些奇特结构进行各种癌症靶向治疗的潜力。G-四链体是四种鸟嘌呤最常见且研究最多的排列方式；然而，也有报道称存在其他可能的非经典核碱基排列方式。在此，我们使用凝胶电泳、圆二色性、紫外和圆二色性热变性方法以及核磁共振，表明端粒（TAG）的双重复序列显示出一种结构转变，即从非经典的分子内三链体转变为除反平行G-四链体之外的非传统四链体。这种转变是由Na阳离子浓度从0.1 M增加到1.0 M介导的，并且该四链体通过非经典/错配碱基对（G∗G、G∗T和T∗T）的氢键环状阵列而相当稳定。有趣的是，在存在K离子的情况下并未表现出这种结构转变。据我们所知，迄今为止尚未有人提出端粒序列中存在这种阳离子特异性的非经典结构转变。
