ORIGINAL ARTICLE Formation of G-wires, bimolecular and tetramolecular quadruplex: Cation-induced structural polymorphs of G-rich DNA sequence of human SYTX gene Saami Ahmed 1 | Mahima Kaushik 1,2 | Swati Chaudhary 1 | Shrikant Kukreti 1 1 Nucleic Acids Research Lab, Department of Chemistry, University of Delhi, Delhi 110007, India 2 Cluster Innovation Centre, University of Delhi, Delhi, India Correspondence Shrikant Kukreti, Department of Chemistry, University of Delhi, Delhi 110007, India. Email: skukreti@chemistry.du.ac.in, kukretishrikant@yahoo.com, and shrikant. kukreti6@gmail.com Funding information University of Delhi Abstract An exceptional property of auto-folding into a range of intra- as well as intermolecular quadru- plexes by guanine-rich oligomers (GROs) of promoters, telomeres and various other genomic locations is still one of the most attractive areas of research at present times. The main reason for this attention is due to their established in vivo existence and biological relevance. Herein, the structural status of a 20-nt long G-rich sequence with two G5 stretches (SG20) is investigated using various biophysical and biochemical techniques. Bioinformatics analysis suggested the pres- ence of a 17-nt stretch of this SG20 sequence in the intronic region of human SYTX (Synaptotagmin 10) gene. The SYTX gene helps in sensing out the Ca 21 ion, causing its intake in the pre-synaptic neuron. A range of various topologies like bimolecular, tetramolecular and guanine-wires (nano-wires) was exhibited by the studied sequence, as a function of cations (Na 1 / K 1 ) concentration. UV-thermal denaturation, gel electrophoresis, and circular dichroism (CD) spec- troscopy showed correlations and established a cation-dependent structural switch. The G-wire formation, in the presence of K 1 , may further be explored for its possible relevance in nano- biotechnological applications. KEYWORDS bimolecular quadruplex, circular dichroism of DNA, G-wire, guanine-quadruplex, polyacrylamide gel electrophoresis, structural polymorphism 1 | INTRODUCTION Guanine-rich oligonucleotides (GROs) of DNA are well known for having the potential to form guanine-quadruplex enabling them to exhibit struc- tural polymorphism in addition to classical Watson and Crick B-form. Based on thermodynamics and kinetic aspects, various polymorphic structures have been acquired by GROs such as G-triplex, G-wire, Tri-G- quadruplex, 3 1 1 quadruplex and so forth. [1] The G-quartet forming abil- ity of G-rich sequences at in vitro physiological conditions and their in vivo significance is now well established. [2,3] Several proteins showing G-quadruplex recognition have also been reported in recent years. [4] Telomerase, an enzyme in eukaryotes has a potential to renovate the telomeres during chromosome replication and is found in most of the cancerous cells, though missing in normal tissue. [5] The fact that telomer- ase expression may be impeded by G-quadruplex binding compounds via telomeres stabilization has triggered the concerns over quadruplex. [6,7] The G-quartet formation is also involved in restraining the cell prolifera- tion, antisense effect and has a promising therapeutic potential. [8] The other remedial applicability of G-rich oligonucleotides is in curing the can- cer by interrupting the DNA replication, to arrest the cell cycle with very less disturbance to normal somatic tissues. [9] Suppression of transcription of cancer cells by targeting the G-quadruplex formed in the PDGFR-b promoter has been demonstrated by Onel et al. [10] In addition to their biological significance, G-quadruplexes can also be utilized in fabricating the DNA-based nanostructures by bottom-up approach. [11] Depending on various factors such as DNA sequence, strand and salt concentration, temperature, buffer, ligands, and molecu- lar crowding agents, G-quadruplex structures exhibit numerous topolo- gies, [12,13] which pave a way for gene therapy [14,15] and inventing the DNA nanostructures. [16,17] It is well established that the G-quadruplex topology and its stabil- ity is governed by the choice of cations and their concentration. [18,19] Biopolymers. 2018;e23115. https://doi.org/10.1002/bip.23115 wileyonlinelibrary.com/journal/bip V C 2018 Wiley Periodicals, Inc. | 1 of 10 Received: 6 December 2017 | Revised: 7 February 2018 | Accepted: 16 February 2018 DOI: 10.1002/bip.23115