Spectroscopic insights into quadruplexes of five-repeat telomere DNA sequences upon G-block damage

Dvořáková, Zuzana; Vorlı́čková, Michaela; Renčiuk, Daniel

doi:10.1016/j.bbagen.2017.07.019

Cited by 2 publications

(1 citation statement)

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“…The absence of key guanine in PQS, in the reported case the substitution of central G of the first block by thymine, might be compensated by the coordination of water molecules in place of the missing guanine [ 15 ]; the quadruplex is formed, though it is significantly destabilized. In principle, the effect of mutations in PQS in genomic context might be also reduced by replacing either only the affected guanine by another guanine located outside the quadruplex-forming motif [ 16 , 17 ], or by replacing the whole affected G-tract with another [ 18 , 19 , 20 ]. For promoter quadruplexes such G-tract redundancy is quite common [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Diversity of Parallel Guanine Quadruplexes Induced by Guanine Substitutions

Bednářová

Vorlı́čková

Renčiuk

2020

IJMS

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Recently, we reported an inhibitory effect of guanine substitutions on the conformational switch from antiparallel to parallel quadruplexes (G4) induced by dehydrating agents. As a possible cause, we proposed a difference in the sensitivity of parallel and antiparallel quadruplexes to the guanine substitutions in the resulting thermodynamic stability. Reports on the influence of guanine substitutions on the biophysical properties of intramolecular parallel quadruplexes are rare. Moreover, such reports are often complicated by the multimerisation tendencies of parallel quadruplexes. To address this incomplete knowledge, we employed circular dichroism spectroscopy (CD), both as stopped-flow-assisted fast kinetics measurements and end-point measurements, accompanied by thermodynamic analyses, based on UV absorption melting profiles, and electrophoretic methods. We showed that parallel quadruplexes are significantly more sensitive towards guanine substitutions than antiparallel ones. Furthermore, guanine-substituted variants, which in principle might correspond to native genomic sequences, distinctly differ in their biophysical properties, indicating that the four guanines in each tetrad of parallel quadruplexes are not equal. In addition, we were able to distinguish by CD an intramolecular G4 from intermolecular ones resulting from multimerisation mediated by terminal tetrad association, but not from intermolecular G4s formed due to inter-strand Hoogsteen hydrogen bond formation. In conclusion, our study indicates significant variability in parallel quadruplex structures, otherwise disregarded without detailed experimental analysis.

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