Conformational plasticity of DNA secondary structures: probing the conversion between i-motif and hairpin species by circular dichroism and ultraviolet resonance Raman spectroscopies

Abstract

The promoter regions of important oncogenes such as BCL2 and KRAS contain GC-rich sequences that can form distinctive noncanonical DNA structures involved in the regulation of transcription: G-quadruplexes on the...

Microscopic Insight into pH-Dependent Conformational Dynamics and Noncanonical Base Pairing in Telomeric i-Motif DNA

“…It is noteworthy that the formation of the C:C W:W trans base pair within the i-motif core induces increased flexibility and can weaken the repulsive interaction between the imino protons of protonated cytosine. The local solvent structure and ion atmosphere together form an ion hydration shell, which may influence the stability of the i-motif in a subtle manner by changing the energetics of base pairing, stacking, and backbone interactions, which vary with the pH environment. ,,,, Studies of the conformational variability and free energy landscape of the i-motif in different ionic environments at acidic pHs are expected to provide more insight into the ionic concentration dependence stability and unfolding of the i-motif. The global or essential modes elucidated by NMA are functionally significant to the i-motif at different pHs.…”

Emerging roles of i-motif in gene expression and disease treatment

“…The human Bcl-2 gene has two main promoters, P1 and P2, both of which regulate the initiation of gene transcription ( Dexheimer et al, 2006 ). P1 is a GC-rich promoter in which i-motif structures have been reported in vitro ( Amato et al, 2022 ). Previous studies proved that G4 structures provide a negative signal, resulting in the silencing of gene expression ( Brooks and Hurley, 2009 ).…”

“…While studies on the KRAS i-motif are insufficient, it is clear that the C-rich nucleic acid sequences in the KRAS promoter can form i-motifs, which are in a state of dynamic transition with hairpin species ( Manzini et al, 1994 ; Amato et al, 2022 ). HnRNP K can bind selectively to the KRAS i-motif and upregulate KRAS transcription.…”

“…These effects are summarized in Table 1. rich promoter in which i-motif structures have been reported in vitro (Amato et al, 2022). Previous studies proved that G4 structures provide a negative signal, resulting in the silencing of gene expression (Brooks and Hurley, 2009).…”

Effects of Molecular Crowding on the Structure, Stability, and Interaction with Ligands of G-quadruplexes

“…However, some research on G4s under physiological conditions has been conducted in environments that simulate molecular crowding. − As a molecular crowding reagent for simulating the intracellular environment, it is required to increase the rejection volume, alter the water activity, and meet the requirement of not interacting directly with nucleic acids and the ligand. To achieve a purposeful study on the conformation of G4s and ligands, many reagents are used to simulate the molecularly crowded environment, such as poly­(ethylene glycol) (PEG), acetonitrile, glycerol, dextran, glucose, and dimethyl sulfoxide (DMSO), etc. ,− PEG with different molecular weights (PEG 200, PEG 400, PEG 2000, and PEG 8000) is commonly adopted to mimic the crowded cellular environment because it is water-soluble, is chemically inert, and does not interact efficiently with biological macromolecules. Moreover, different molecular weights of PEG can be obtained by changing the degree of polymerization, thus allowing the simulation of molecules of different sizes in living organisms and better representing the intracellular environment. , Changing the external environment and the metabolic activities of cells will inevitably affect the physicochemical properties of the internal environment, such as pH, osmolarity, and temperature, at all times.…”