Na selective structural switch from an intramolecular triplex to tetrad stabilised by non-canonical mispairs in double repeat of telomere (TAG).

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.