Stability and Structure of Telomeric DNA Sequences Forming Quadruplexes Containing Four G-Tetrads with Different Topological Arrangements

Abstract

Telomeres are DNA-protein structures at the ends of eukaryotic chromosomes, the DNA of which comprise noncoding repeats of guanine-rich sequences. Telomeric DNA plays a fundamental role in protecting the cell from recombination and degradation. Telomeric sequences can form quadruplex structures stabilized by guanine quartets. These structures can be constructed from one, two, or four oligonucleotidic strands. Here, we report the thermodynamic characterization of the stability, analyzed by differential scanning calorimetry, of three DNA quadruplexes of different molecularity, all containing four G-tetrads. The conformational properties of these quadruple helices were studied by circular dichroism. The investigated oligomers form well-defined G-quadruplex structures in the presence of sodium ions. Two have the truncated telomeric sequence from Oxytricha, d(TGGGGT) and d(GGGGTTTTGGGG), which form a tetramolecular and bimolecular quadruplex, respectively. The third sequence, d(GGGGTTGGGGTGTGGGGTTGGGG) was designed to form a unimolecular quadruplex. The thermodynamic parameters of these quadruplexes have been determined. The tetramolecular structure is thermodynamically more stable than the bimolecular one, which, in turn, is more stable than the unimolecular one. The experimental data were discussed in light of the molecular-modeling study.

Characterization of parallel and antiparallel G-tetraplex structures by vibrational spectroscopy

“…In addition we can notice the emergence of an absorption at 920 cm -1 which may reflect the existence of guanosines in syn conformation. Such a band had been previously observed in the left-handed Z form spectra and is probably related to a C-N vibration in syn guanosines [44]. .…”

Energetic aspects of locked nucleic acids quadruplex association and dissociation

“…These spectra are consistent with the parallel-stranded quadruplex structures. 17,35 The spectrum of the LNA sequence presents an additional positive band at 288 nm, and this unusual band can be associated with the presence of the quadruplex structure. 25 We found that the melting and annealing curves for all the sequences show hystheresis.…”

Structural properties and the effect of 2,6‐diaminoanthraquinone on G‐tetrad, non‐G‐tetrads, and mixed tetrads—A density functional theory study

“…In G-tetrad, the Guanine bases are linked through Hoogsteen pairing or by bifurcated hydrogen bonds between N1-H, N2-H, and O6 atoms as reported in [23][24][25][26][27][28][50][51][52]. Guanine tetrad is formed between the donor and acceptor atoms (see Fig.…”