Crosstalk between G-quadruplex and ROS

Abstract

The excessive production of reactive oxygen species (ROS) can lead to single nucleic acid base damage, DNA strand breakage, inter- and intra-strand cross-linking of nucleic acids, and protein-DNA cross-linking involved in the pathogenesis of cancer, neurodegenerative diseases, and aging. G-quadruplex (G4) is a stacked nucleic acid structure that is ubiquitous across regulatory regions of multiple genes. Abnormal formation and destruction of G4s due to multiple factors, including cations, helicases, transcription factors (TFs), G4-binding proteins, and epigenetic modifications, affect gene replication, transcription, translation, and epigenetic regulation. Due to the lower redox potential of G-rich sequences and unique structural characteristics, G4s are highly susceptible to oxidative damage. Additionally, the formation, stability, and biological regulatory role of G4s are affected by ROS. G4s are involved in regulating gene transcription, translation, and telomere length maintenance, and are therefore key players in age-related degeneration. Furthermore, G4s also mediate the antioxidant process by forming stress granules and activating Nrf2, which is suggestive of their involvement in developing ROS-related diseases. In this review, we have summarized the crosstalk between ROS and G4s, and the possible regulatory mechanisms through which G4s play roles in aging and age-related diseases.

Epithelial–mesenchymal plasticity in kidney fibrosis

“…In addition to the stimuli described above, reactive oxygen species (ROS) is a potent inducer mediating EMT particularly in peritubular microenvironment (Figure 3). The increased level of intracellular ROS can cause oxidation of lipids, DNAs, and proteins, leading to cell damage/injury (Ming et al, 2022; Wu et al, 2023). ROS also acts as a secondary messenger in cellular signaling pathways (Ming et al, 2022; Wu et al, 2023).…”

“…The increased level of intracellular ROS can cause oxidation of lipids, DNAs, and proteins, leading to cell damage/injury (Ming et al, 2022; Wu et al, 2023). ROS also acts as a secondary messenger in cellular signaling pathways (Ming et al, 2022; Wu et al, 2023). When ROS increases in TECs, the cells release proinflammatory cytokines and chemokines for repairing mechanism.…”

“…When ROS increases in TECs, the cells release proinflammatory cytokines and chemokines for repairing mechanism. Nevertheless, uncontrolled or prolonged ROS production results in inflammation and fibrosis (Ming et al, 2022; Wu et al, 2023). All the stimuli mentioned above and several other factors can induce intracellular ROS overproduction in kidney tissue.…”

Effect of Different Edible Trichosanthes Germplasm on Its Seed Oil to Enhance Antioxidant and Anti-Aging Activity in Caenorhabditis elegans

“…Aging is a major risk factor for most neurodegenerative diseases, including Alzheimer's disease [14]. The reactive oxygen species (ROS) produced during the metabolic process is one of the main causes of aging [15]. Hence, there is a growing need to find compounds with antioxidant properties, low toxicity, and minimal side effects to combat aging.…”

G-quadruplexes and associated proteins in aging and Alzheimer’s disease

“…If antioxidants are limited or depleted in the brain, the neuronal cells are more susceptible to ROS-induced DNA damage ( Hirano et al, 1996 ; Kaneko et al, 1996 ; Fleming and Burrows, 2020 ). The oxidative DNA damage is increased in genes that are rich in G-rich sequences and have the propensity to form G4-DNA motifs ( Brosh and Bohr, 2007 ; Bielskute et al, 2021 ; Wu et al, 2023 ). In humans, premature aging and early death are characteristics of rare heritable diseases that are linked to defects in DNA repair or the processing of DNA damage that involves the dysregulation of RecQ helicases that regulate G4 structures ( Liano et al, 2021 ).…”