Structural Polymorphism of Telomeric DNA Regulated by pH and Divalent Cation

Abstract

DNA oligonucleotides can form multi-stranded structures such as a duplex, triplex, and quadruplex, while the double helical structure is generally considered as the canonical structure of DNA oligonucleotides. Guanine-rich or cytosine-rich oligonucleotides, which are observed in telomere, centromere, and other biologically important sequences in vivo, can form four-stranded G-quadruplex and I-motif structures in vitro. In this study, we have investigated the effects of pH and cation on the structures and their stabilities of d(G4T4G4) and d(C4A4C4). The CD spectra and thermal melting curves of DNAs at various pHs demonstrated that acidic conditions induced a stable I-motif structure of d(C4A4C4), while the pH value did not affect the G-quadruplex structure and stability of d(G4T4G4). The CD spectra of the 1:1 mixture of d(G4T4G4) and d(C4A4C4) indicated that the acidic conditions inhibit the duplex formation between d(G4T4G4) and d(C4A4C4). Isothermal titration calorimetry measurements of the duplex formation at various pHs also quantitatively indicated that the acidic conditions inhibit the duplex formation. On the other hand, the CD spectra and thermal melting curves of DNAs in the absence and presence of Ca2+ indicated that Ca2+ induces a parallel G-quadruplex structure of d(G4T4G4) and then inhibits the duplex formation. These results lead to the conclusion that both the pH and coexisting cation can induce and regulate the structural polymorphisms the oligonucleotides in which they form the G-quadruplex, I-motif, and duplex depending on the conditions. Thus, the results reported here indicate pivotal roles of pH and coexisting cations in biological processes by regulating the conformational switching between the duplex and quadruplexes structures of the guanine-rich or cytosine-rich oligonucleotides in vivo.

New Insights into Transcription Fidelity: Thermal Stability of Non-Canonical Structures in Template DNA Regulates Transcriptional Arrest, Pause, and Slippage

“…We evaluated transcription in buffer with KCl concentrations ranging from 0 to 70 mM (Figure 3), because the stability of G-quadruplex strongly depends on K+ concentration [30], [31], [32]. UV measurements showed the −Δ G o 37 values of q5 increased with increasing KCl concentration (Table S4 in File S1).…”

Quadruplex-Forming Oligonucleotides as Tools in Anticancer Therapy and Aptamers Design: Energetic Aspects

“…Its structure elucidation will depend on the relative stability of the quandruplex. Further, small changes in the sequence and/or solution conditions can have profound effects on the folding and the thermodynamic stability of the resulting quadruplex [132,133].…”

Dynamic Structures of DNA Heptamers with Different Central Trinucleotide Sequences Studied by Electrochemical and Spectral Methods

“…Guanine‐rich or cytosine‐rich oligonucleotides (ODNs) occurring in telomere, centromere and other biologically important sequences in vivo are capable of forming four‐stranded G‐quadruplex or i‐motif structures in vitro 14. G‐quadruplexes are stabilized by G‐quartets which are formed by four guanine molecules bound by Hoogsteen hydrogen bonds in coplanar arrangement 14. The G‐quadruplexes are formed in the presence of some cations, such as Na + and especially K + .…”

“…The complementary cytosine‐rich DNA fragments form tetrameric inter‐ or intramolecular structures, known as i‐motif, whose basic building block is the hemiprotonated C . C + base‐pair 14–18. The i‐motif structures are formed in acidic pHs, but also in solutions close to neutral pH values 14.…”

“…C + base‐pair 14–18. The i‐motif structures are formed in acidic pHs, but also in solutions close to neutral pH values 14. Formation of i‐motif structures is linked with various diseases, e.g.…”