Reverse Watson–Crick G–G base pair in G-quadruplex formation

Abstract

A stable intermediate dimeric G-rich form as a precursor of tetrameric G-quadruplex structures has been detected via MALDI-TOF spectrometry. Molecular dynamics simulation offered detailed insights at the atomic level, assigning reverse Watson-Crick G-G base pairing (not Hoogsteen) in the G-rich dimer. In support of this, cisplatin formed a stable adduct by binding to the dimeric G-rich structure, eliminating the possibility of G-G Hoogsteen hydrogen bond formation.

Molecular Dynamics Simulations of the c-kit1 Promoter G-Quadruplex: Importance of Electronic Polarization on Stability and Cooperative Ion Binding

“…The base dipole moments of guanine, thymine, and adenine were all shifted up in c-kit1 relative to B-DNA, whereas cytosine base dipole moments were unchanged (Supporting Information, Table S2). Such changes in base polarization suggest that bases in the c-kit1 GQ have fundamentally different electronic structures from those of B-DNA because of differences in π−π stacking of tetrads, hydrogen bonding (Hoogsteen vs Watson−Crick), 88 and the specific coordination of K + in the GQ stem. This outcome emphasizes the importance of using a polarizable FF to simulate GQs; that is, the partial charge assignment in additive FFs will fail to account for alterations to the electronic structure that are inherent as DNA adopts the GQ fold.…”

The Research of G–Motif Construction and Chirality in Deoxyguanosine Monophosphate Nucleotide Complexes

“…A novel guanine–guanine base mismatch pattern with unusual ( high anti )—( high anti ) type of arrangement around the glycosidic angle conformations was successfully constructed. This base pair is different from GG Hoogsteen base pairs and reverse Watson–Crick GG mismatched base pairing ( Mondal et al, 2016 ) 7 , but is similar to hemiprotonated CC+ and AA base pairs in i–motif and A–motif, respectively. So, we named it g–motif in this work.…”

“…The non–B-DNA secondary structures ( Afek et al, 2020 ; Xiong et al, 2021 ), which are folded in a different manner from B-DNA or form unnatural base pairs that are not used for Watson–Crick (G≡C and A = T) base pairing ( Watson and Crick, 1953 ; Brovarets’ et al, 2018 ), can induce genetic instability and cause a variety of human diseases ( Brovarets’ et al, 2019 ; Li et al, 2020 ). However, the research of mismatched base-pairing interactions has great significance because they play an important role in various processes related to the biological function of nucleic acids ( Iyer et al, 2006 ; Granzhan et al, 2014 ; Mondal et al, 2016 ), helping to reveal genetic diseases caused by the non–B-DNA structures. In biological systems, for example, aberrant amplification of the hexanucleotide GGGGCC (G4C2) repeated in the human C9ORF72 gene is the most common genetic factor found behind frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) ( DeJesus-Hernandez et al, 2011 ).…”

Cation-responsive and photocleavable hydrogels from non-canonical amphiphilic DNA nanostructures

“…This trend is consistent with previous literature reports, 46,51,52 and can be rationalised as the result of a nucleation-zipping assembly pathway. 53,54 Within this framework, longer G-runs could afford increased stability to transient dimers and trimers hypothesised as intermediates in the G4 assembly pathway, 55,56 hence boosting folding kinetics. In Figure 2b-(i) we explore the dependency of t 1/2 on Quad-Star concentration and, expectedly, we observe a steeply decreasing power-law trend that allows us to extract the reaction order of the assembly process as n = 3.605±0.740 for 5G (R 2 = 0.911) and n = 3.711 ± 0.127 (R 2 = 0.996) for 6G, both values closely matching the expected stoichiometric value of 4.…”