Crosstalk between G-quadruplex and ROS
Open accessAbstract
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.
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G4s are highly susceptible to oxidative damage, as G-rich sequences have a low redox-potential and thus can act as ROS-sinks.
“Furthermore, G4s are highly susceptible to oxidative damage, as G-rich sequences have a low redox-potential and thus can act as ROS-sinks (84).”
From G-quadruplex-mediated genomic instability drives SNVs in cancer (2024) · cites this paper as [84]
The Introduction says guanine has a low redox potential, and the “ROS and G4S” section says G4s are highly susceptible to ROS-mediated oxidative damage because they are G-rich. The paper suggests that greater G4 stability may increase the antioxidant capacity of telomeres, but it does not establish that G4s generally act as ROS sinks. (LLM, conf=0.82)
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A guide to computational methods for G-quadruplex prediction
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“In addition to DNA G4s, RNA G4s are also involved in several biological processes, such as telomere homeostasis, mRNA localization, 3-terminal processing, alternative splicing, and translation regulation [153].”
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G4Hunter web application: a web server for G-quadruplex prediction
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The role of m6A modification in physiology and disease
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“They are activated by light or laser irradiation at a specific wavelength, producing ROS that triggers tumor cell death via apoptosis or necrosis [175].”
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“The guanines are frequently oxidized in aged cells and stabilize the G4 structure, making these non-canonical structures an attractive therapeutic target for neurodegenerative disorders [94].”
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“In an in vitro study, ROS increased the transcriptional activity of VEGF via its promoter G4, which was blocked in the presence of a G4 ligand [168].”
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G-quadruplex unwinding helicases and their function <i>in vivo</i>
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“The unfolding and folding of G4s during replication or transcription are mainly catalyzed by helicases [54, 55] including DNA G4 helicases such as Pif1, ATRX, RecQ, FANCJ, BLM and WRN [54], and RNA G4 helicases such as DHX9, DHX36, and the DDX5/ DDX17/Dbp2 subfamily [56] (Fig.”
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“Previous reports have demonstrated that ROS induces R-loop formation and facilitate recruitment of R-loop sensors such as RAD52 to the damaged sites [100].”
BackgroundSelective Recognition of G-Quadruplex Telomeric DNA by a Bis(quinacridine) Macrocycle
Teulade‐Fichou, M., Carrasco, C., Guittat, L., Bailly, C., Alberti, P., Mergny, J., David, A., Lehn, J., & Wilson, W. D. (2003) · Journal of the American Chemical Society · doi:10.1021/ja021299j · Cited by 174 · see citing works
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“Furthermore, overexpression of NM23-H2 in the human cancer cell lines HeLa S3 and A549 enhanced c-Myc promoter activity [71].”
BackgroundChemical and structural studies provide a mechanistic basis for recognition of the MYC G-quadruplex
Calabrese, D. R., Chen, X., Leon, E. C., Gaikwad, S. M., Phyo, Z., Hewitt, W. M., Alden, S., Hilimire, T. A., He, F., Michalowski, A. M., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06315-w · Cited by 172 · see citing works
TIA1 oxidation inhibits stress granule assembly and sensitizes cells to stress-induced apoptosis
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Hydrogen peroxide induces stress granule formation independent of eIF2α phosphorylation
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Interplay of Guanine Oxidation and G-Quadruplex Folding in Gene Promoters
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“A recent study demonstrated that guanine oxidation to OG is 3-fold higher in the PQS of gene promoters [126], and some of these regions have the propensity to form G4s [90].”
BackgroundThe Interplay between G-quadruplex and Transcription
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8-Oxo-7,8-dihydroguanine, friend and foe: Epigenetic-like regulator versus initiator of mutagenesis
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“Similarly, other zinc-finger TFs, including MAZ and HSUB1, also promote gene transcription through G4s [66, 67].”
BackgroundStructures of Zinc Finger Domains from Transcription Factor Sp1
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“The same team also found that H2O2 recruits poly [ADP-ribose] polymerase 1 (PARP-1) to KRAS promoter region, wherein it binds to local G4 structures, undergoes auto PARylation and activates KRAS transcription by recruiting MAZ and hnRNPA1 [132, 133] (Fig.”
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“For example, nucleoside (NCL) repress c-Myc and LTR transcription by binding to G4 forming in the gene promoter region and stabilizing its structure [69, 70].”
BackgroundZhou, J., Liu, M., Fleming, A. M., Burrows, C. J., & Wallace, S. S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.479055 · Cited by 130 · cited 1× · see citing works
“reported that while mNEIL3 can excise Tg from G4 DNA, none of the glycosylases (NEIL1, NEIL2, mNEIL3, NTH1, and OGG1) can repair OG residues in quadruplex DNA [124].”
BackgroundAtrx deficiency induces telomere dysfunction, endocrine defects, and reduced life span
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“Treatment of ATRX-null neuro-progenitor cells with G4 ligand increased DNA damage [57].”
BackgroundG-quadruplexes in human promoters: A challenge for therapeutic applications
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“Bioinformatics analyses have shown that G4s are also enriched in the CpG islands in genomic DNA[77, 78].”
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G‐Quadruplex Recognition by Quinacridines: a SAR, NMR, and Biological Study
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Sorafenib, a multikinase inhibitor, induces formation of stress granules in hepatocarcinoma cells
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“Thus, developing targeted drugs stabilizing SGs have been a new promising direction in cancer therapeutics [147].”
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“In the presence of hemin, telomeres can fold into G4 structures with catalytic oxidation properties in vivo [192].”
BackgroundA guide to computational methods for G-quadruplex prediction
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eIF4G has intrinsic G-quadruplex binding activity that is required for tiRNA function
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“The HEAT1 region of the eIF4G protein is the main binding region of the G4-tiRNA complex [143].”
BackgroundG-Quadruplex Binding Ligands: from Naturally Occurring to Rationally Designed Molecules
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Potential Roles for G-Quadruplexes in Mitochondria
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“G-quadruplex (G4) is a four-stranded nucleic acid structure formed by guanine-rich DNA and RNA sequences with Hoogsteen hydrogen bonding [11, 12].”
BackgroundGuanine quadruplex DNA structure restricts methylation of CpGdinucleotidesgenome-wide
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“For example, Cells treated with a mild dose of H2O2 show a significant increase in cytosolic G4s, which co-localize SH-related marker proteins [23].”
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Impact of Oxidative Lesions on the Human Telomeric G-Quadruplex
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Superoxide radicals have a protective role during H 2 O 2 stress
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Oxidative Stress: Role and Response of Short Guanine Tracts at Genomic Locations
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G-quadruplexes Sequester Free Heme in Living Cells
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8‐Oxoguanine in a quadruplex of the human telomere DNA sequence
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Structural Insight into the interaction of Flavonoids with Human Telomeric Sequence
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Targeting G-quadruplex nucleic acids with heterocyclic alkaloids and their derivatives
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An anionic phthalocyanine decreases NRAS expression by breaking down its RNA G-quadruplex
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“G4 ligand Target G4 Gene Cell type Porphyrin derivatives TMPyP4 [105, 177, 182, 231] DNA KRAS MCF-7 human breast cancer cells、HeLa cells TMPipEOPP [179] DNA human colon carcinoma cells (HCT-8) ZnP1 [180] DNA TMPyP4-C14 [106] RNA KRAS, NRAS pancreatic cancer cells Phthalocyanine derivatives ZnAPC [181] RNA NRAS MCF-7 h…”
BackgroundSmall-molecule G-quadruplex stabilizers reveal a novel pathway of autophagy regulation in neurons
Moruno-Manchon, J. F., Lejault, P., Wang, Y., McCauley, B. S., Honarpisheh, P., Morales‐Scheihing, D., Singh, S. S., Dang, W., Kim, N., Urayama, A., et al. (2020) · eLife · doi:10.7554/elife.52283 · Cited by 80 · cited 2× · see citing works
“Overexpressing Pif1 in neurons rescued phenotypes associated with PDS treatment and increased autophagy [39].”
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“Computational predictions indicated that TFs are strongly enriched in the G4 motifs of promoters across genomes of multiple species, and dozens of these TFs appear to be conserved [60, 63].”
BackgroundHuman MYC G-quadruplex: From discovery to a cancer therapeutic target
Wang, W., Hu, S., Gu, Y., Yan, Y., Stovall, D. B., Li, D., & Sui, G. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188410 · Cited by 76 · cited 12× · see citing works
“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.”
BackgroundInfluentialDirectly lighting up RNA G-quadruplexes from test tubes to living human cells
Xu, S., Li, Q., Xiang, J., Yang, Q., Sun, H., Guan, A., Wang, L., Liu, Y., Yu, L., Shi, Y., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1040 · Cited by 75 · see citing works
Specific G-quadruplex ligands modulate the alternative splicing of Bcl-X
Weldon, C., Dacanay, J., Gokhale, V. M., Boddupally, P. V. L., Behm‐Ansmant, I., Burley, G. A., Branlant, C., Hurley, L. H., Dominguez, C., & Eperon, I. C. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1122 · Cited by 73 · see citing works
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“Recent studies show that G4s can directly produce guanine radicals induced by UV irradiation, leading to DNA damage [103, 104].”
BackgroundSaha, D., Singh, A., Hussain, T., Srivastava, V. K., Sengupta, S., Kar, A., Dhapola, P., Dhople, V. M., Ummanni, R., & Chowdhury, S. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.792077 · Cited by 72 · cited 2× · see citing works
“It binds to the G4 within the hTERT promoter and recruits epigenetic modifiers such as REST, co-REST, and LSD1 to form an epigenetic repressor complex, thereby inhibiting hTERT gene transcription [73].”
BackgroundHuman NEIL3 Gene Expression Regulated by Epigenetic-Like Oxidative DNA Modification
Fleming, A. M., Zhu, J., Manage, S. A. H., & Burrows, C. J. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b01847 · Cited by 72 · cited 1× · see citing works
“Activation of NEIL3 expression through this proposed mechanism allows cells to respond to mutagenic DNA damage induced by oxidative or inflammatory stress [131].”
BackgroundG-Quadruplex loops regulate PARP-1 enzymatic activation
Edwards, A. D., Marecki, J. C., Byrd, A. K., Gao, J., & Raney, K. D. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa1172 · Cited by 72 · cited 1× · see citing works
“In fact, the G4 forming sequence in the promoter of the proto-oncogene c-kit stimulates the enzymatic activity of PARP-1, which is dependent on the loop features and oxidative damage [134].”
BackgroundSeifermann, M., & Epe, B. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.11.018 · Cited by 71 · cited 1× · see citing works
“For example, OG formation in the G4s of the PCNA promoter increased gene expression [127, 128].”
BackgroundChen, H., Long, H., Cui, X., Zhou, J., Xu, M., & Yuan, G. (2014) · Journal of the American Chemical Society · doi:10.1021/ja412128w · Cited by 70 · cited 1× · see citing works
“G4 structures are present in the HIF1α promoter and the 5′UTR [170, 171] and inhibit HIF1α transcription by blocking AP2 binding [172].”
BackgroundMolecular mechanisms by which oxidative DNA damage promotes telomerase activity
Lee, H.-T., Bose, A., Lee, C.-Y., Opresko, P. L., & Myong, S. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx789 · Cited by 69 · cited 2× · see citing works
“Oxidative DNA damage can increase telomerase activity by destabilizing DNA G4 structures [120].”
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“The 5′UTR of Nrf2 mRNA can form G4, which interacts with EF1a and promotes de novo Nrf2 protein translation under H2O2 stress [155].”
BackgroundFleming, A. M., Zhu, J., Ding, Y., Visser, J. A., Zhu, J., & Burrows, C. J. (2018) · Biochemistry · doi:10.1021/acs.biochem.7b01172 · Cited by 64 · see citing works
Direct visualization of nucleolar G-quadruplexes in live cells by using a fluorescent light-up probe
Zhang, S., Sun, H., Chen, H., Li, Q., Guan, A., Wang, L., Shi, Y., Xu, S., Liu, M., & Tang, Y. (2018) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2018.01.022 · Cited by 63 · see citing works
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“TMPyP4-C14 [106] RNA KRAS, NRAS pancreatic cancer cells”
BackgroundAn Improved Model for the hTERT Promoter Quadruplex
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Recognition of G-quadruplex RNA by a crucial RNA methyltransferase component, METTL14
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“However, G4-forming regions in many DRACH sequences can directly recruit METTL3/METTL14 to specific methylation sites in their vicinity [87].”
BackgroundConstitutive translation of human α-synuclein is mediated by the 5′-untranslated region
Koukouraki, P., & Doxakis, E. (2016) · Open Biology · doi:10.1098/rsob.160022 · Cited by 58 · see citing works
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“A recent study showed that poly-G4-TMPyP4 complexes generate high levels of singlet oxygen at cancer lesions in response to UV irradiation and promote apoptosis of tumor cells [176].”
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“ROS can affect the formation or dissociation of G4 motifs by reducing their thermal stability, altering the original G4 structural pattern, and influencing other chromatin structures at transcriptionally active sites such as R-loops and D-loops.”
BackgroundTan, J. J., Wang, X., Phoon, L. Y., Yang, H., & Lan, L. (2020) · FEBS Letters · doi:10.1002/1873-3468.13738 · Cited by 56 · cited 4× · see citing works
“ROS can affect the formation or dissociation of G4 motifs by reducing their thermal stability, altering the original G4 structural pattern, and influencing other chromatin structures at transcriptionally active sites such as R-loops and D-loops.”
BackgroundInfluentialNaguib, S. A., Backstrom, J. R., Gil, M., Calkins, D. J., & Rex, T. S. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101883 · Cited by 56 · see citing works
RNA G-quadruplex regulates microRNA-26a biogenesis and function
Liu, G., Du, W., Xu, H., Sun, Q., Tang, D., Zou, S., Zhang, Y., Ma, M., Zhang, G., Du, X., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.02.032 · Cited by 55 · cited 2× · see citing works
“DHX36 is an RNA helicase that binds to and unwinds pri-miR-26a RNA G4 structure and thus regulates miR-26a biogenesis and function in hepatic lipid metabolism and insulin sensitivity [44].”
BackgroundMethodDai, J., Liu, Z.-Q., Wang, X., Lin, J., Yao, P.-F., Huang, S., Ou, T., Tan, J., Li, D., Gu, L., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00139 · Cited by 55 · see citing works
DNA G‐quadruplexes show strong interaction with DNA methyltransferases in vitro
Cree, S. L., Fredericks, R., Miller, A. L., Pearce, F. G., Filichev, V. V., Fee, C. J., & Kennedy, M. A. (2016) · FEBS Letters · doi:10.1002/1873-3468.12331 · Cited by 55 · see citing works
The Effect of Nrf2 Pathway Activation on Human Pancreatic Islet Cells
Masuda, Y., Vaziri, N. D., Li, S., Le, A., Hajighasemi‐Ossareh, M., Robles, L. Y., Foster, C. E., Stamos, M. J., Al-Abodullah, I., Ricordi, C., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131012 · Cited by 54 · cited 1× · see citing works
“G4 and Nrf2 Low to moderate levels of oxidative stress activate antioxidant and detoxification genes that contain the antioxidant response element (ARE) in their promoters, which is the binding site of the Nrf2 transcription factor [148, 149].”
BackgroundRedstone, S. C. J., Fleming, A. M., & Burrows, C. J. (2019) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.8b00332 · Cited by 54 · cited 4× · see citing works
“G4-sequencing has further revealed that G4s are highly enriched in the promoters and TSSs of human and mouse genes [35].”
BackgroundInfluentialUnusual −1 Ribosomal Frameshift Caused by Stable RNA G-Quadruplex in Open Reading Frame
Endoh, T., & Sugimoto, N. (2013) · Analytical Chemistry · doi:10.1021/ac402497x · Cited by 53 · see citing works
G-quadruplex Stabilization Fuels the ALT Pathway in ALT-positive Osteosarcoma Cells
Amato, R., Valenzuela, M., Berardinelli, F., Salvati, E., Maresca, C., Leone, S., Antoccia, A., & Sgura, A. (2020) · Genes · doi:10.3390/genes11030304 · Cited by 53 · see citing works
Evidence for G-quadruplex in the promoter of vegfr-2 and its targeting to inhibit tumor angiogenesis
Salvati, E., Zizza, P., Rizzo, A., Iachettini, S., Cingolani, C., D’Angelo, C., Porru, M., Randazzo, A., Pagano, B., Novellino, E., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1289 · Cited by 52 · see citing works
Fleming, A. M., Zhu, J., Ding, Y., & Burrows, C. J. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz207 · Cited by 52 · cited 1× · see citing works
“Established G4s occur naturally in a similar location relative to the TSS for possible oxidation-induced gene activation [129].”
BackgroundG-quadruplex binder pyridostatin as an effective multi-target ZIKV inhibitor
Zou, M., Li, J., Zhang, M.-J., Li, J., Huang, J.-T., You, P.-D., Liu, S., & Zhou, C. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.08.121 · Cited by 52 · see citing works
Self-citationOxidative lesions modulate G-quadruplex stability and structure in the human BCL2 promoter
Bielskutė, S., Plavec, J., & Podbevšek, P. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab057 · Cited by 52 · cited 1× · see citing works
“Another study showed that OG could enhance the stability of the G4 structure located in the promoter region of the BCL2, which suggests a potential novel regulatory role of oxidative stress in general, and specifically in BCL2 gene transcription [97].”
BackgroundEspejo, M. A. J., & Line, S. R. P. (2019) · FEBS Journal · doi:10.1111/febs.15065 · Cited by 51 · cited 1× · see citing works
“Computational analyses have shown that hypermethylated CpG tends to be associated with low G4 stability [59].”
BackgroundGuanine Radicals Induced in DNA by Low-Energy Photoionization
Balanikas, E., Bányász, Á., Douki, T., Baldacchino, G., & Markovitsi, D. (2020) · Accounts of Chemical Research · doi:10.1021/acs.accounts.0c00245 · Cited by 51 · see citing works
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Kazemier, H. G., Paeschke, K., & Lansdorp, P. M. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx245 · Cited by 50 · see citing works
DNA damage processing at telomeres: The ends justify the means
Fouquerel, E., Parikh, D., & Opresko, P. L. (2016) · DNA repair · doi:10.1016/j.dnarep.2016.05.022 · Cited by 48 · see citing works
Gao, J., Zybailov, B. L., Byrd, A. K., Griffin, W. C., Chib, S., Mackintosh, S. G., Tackett, A. J., & Raney, K. D. (2015) · Chemical Communications · doi:10.1039/c5cc00742a · Cited by 47 · cited 1× · see citing works
“Similarly, other zinc-finger TFs, including MAZ and HSUB1, also promote gene transcription through G4s [66, 67].”
BackgroundHoriuchi, K., Kawamura, T., & Hamakubo, T. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101248 · Cited by 44 · see citing works
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“H2O2 decomposes in the presence of Fe into CO3 and HO, of which the former is a highly potent oxidizer [89].”
BackgroundCaterino, M., D’Aria, F., Kustov, A. V., Belykh, D. V., Khudyaeva, I. S., Starseva, O. M., Березин, Д. Б., Игоревна, П. Я., Усачева, Т. Р., Amato, J., et al. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.12.152 · Cited by 42 · cited 10× · see citing works
“A recent study showed that poly-G4-TMPyP4 complexes generate high levels of singlet oxygen at cancer lesions in response to UV irradiation and promote apoptosis of tumor cells [176].”
BackgroundInfluentialUp-Regulating Relaxin Expression by G-Quadruplex Interactive Ligand to Achieve Antifibrotic Action
Gu, H., Lin, S., Xu, M., Yu, H., Du, X., Zhang, Y., Yuan, G., & Gao, W. D. (2012) · Endocrinology · doi:10.1210/en.2012-1114 · Cited by 41 · see citing works
Epigenetic Modulation of Chromatin States and Gene Expression by G-Quadruplex Structures
Reina, C., & Cavalieri, V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21114172 · Cited by 41 · see citing works
G-Quadruplex Modulation of SP1 Functional Binding Sites at the KIT Proximal Promoter
Ros, S. D., Nicoletto, G., Rigo, R., Ceschi, S., Zorzan, E., Dacasto, M., Giantin, M., & Sissi, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010329 · Cited by 40 · see citing works
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Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules
Singh, K., Lin, J., Lecomte, N., Mohan, P., Gokce, A., Sanghvi, V. R., Jiang, M., Grbovic-Huezo, O., Burčul, A., Stark, S. G., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-2929 · Cited by 39 · cited 12× · see citing works
“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.”
BackgroundInfluentialCui, X., Lin, S., & Yuan, G. (2012) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2012.02.029 · Cited by 37 · see citing works
Stabilization of G-quadruplex DNA and inhibition of Bcl-2 expression by a pyridostatin analog
Feng, Y., Yang, D., Chen, H., Cheng, W., Wang, L., Sun, H., & Tang, Y. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.02.065 · Cited by 37 · see citing works
RHPS4 G-Quadruplex Ligand Induces Anti-Proliferative Effects in Brain Tumor Cells
Lagah, S., Tan, I., Radhakrishnan, P., Hirst, R. A., Ward, J. H., O’Callaghan, C., Smith, S. J., Stevens, M. F. G., Grundy, R. G., & Rahman, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086187 · Cited by 35 · see citing works
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Structural analysis and cellular visualization of APP RNA G-quadruplex
Lyu, K., Chen, S.-B., Chan, C., Tan, J., & Kwok, C. K. (2019) · Chemical Science · doi:10.1039/c9sc02768h · Cited by 35 · see citing works
Guillon, J., Cohen, A., Boudot, C., Valle, A., Milano, V., Das, R. N., Guédin, A., Moreau, S., Ronga, L., Savrimoutou, S., et al. (2020) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2019.1706502 · Cited by 35 · see citing works
Wen, L., & Xie, M. (2016) · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2016.08.013 · Cited by 33 · see citing works
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Regulation of autophagy by DNA G-quadruplexes
Lejault, P., Moruno-Manchon, J. F., Vemu, S. M., Honarpisheh, P., Zhu, L., Kim, N., Urayama, A., Monchaud, D., McCullough, L. D., & Tsvetkov, A. S. (2020) · Autophagy · doi:10.1080/15548627.2020.1769991 · Cited by 31 · see citing works
Action and function of helicases on RNA G-quadruplexes
Caterino, M., & Paeschke, K. (2021) · Methods · doi:10.1016/j.ymeth.2021.09.003 · Cited by 31 · cited 1× · see citing works
“The unfolding and folding of G4s during replication or transcription are mainly catalyzed by helicases [54, 55] including DNA G4 helicases such as Pif1, ATRX, RecQ, FANCJ, BLM and WRN [54], and RNA G4 helicases such as DHX9, DHX36, and the DDX5/ DDX17/Dbp2 subfamily [56] (Fig.”
BackgroundRocca, R., Moraca, F., Costa, G., Alcaro, S., Distinto, S., Maccioni, E., Ortuso, F., Artese, A., & Parrotta, L. (2014) · Molecules · doi:10.3390/molecules20010206 · Cited by 31 · see citing works
Zhao, N., Ding, B., Zhang, Y., Klockow, J., Lau, K., Chin, F. T., Cheng, Z., & Liu, H. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.05.031 · Cited by 30 · see citing works
Aptamer Selection Based on G4-Forming Promoter Region
Yoshida, W., Saito, T., Yokoyama, T., Ferri, S. R., & Ikebukuro, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065497 · Cited by 30 · cited 5× · see citing works
“In fact, its constituent structure involves multiple TFs and other binding proteins such as eIF protein family (eIF2, eIF4G), T-cell intracellular antigen1 (TIA1), Y-box binding protein 1 (YB-1), USP10 and G3BP1 [135–138].”
BackgroundInfluentialDinçer, Y., Akkaya, Ç., Mutlu, T., Yavuzer, S., Erkol, G., Bozluolçay, M., & Güven, M. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134362 · Cited by 30 · cited 1× · see citing works
“A disproportionate level of oxidative stress and an aberrant DDR machinery can lead to accumulated damaged DNA and trigger apoptotic pathways [8], which is the pathological basis of aging and agingrelated diseases [9, 10].”
BackgroundLight-induced oxidation of the telomeric G4 DNA in complex with Zn(II) tetracarboxymethyl porphyrin
Beniaminov, A. D., Новиков, Р. А., Mamaeva, O. K., Mitkevich, V. A., Smirnov, I. P., Livshits, M. A., Shchyolkina, A. K., & Kaluzhny, D. N. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw947 · Cited by 28 · cited 1× · see citing works
“ZnP1 is a cationic porphyrin derivative that binds to the DNA groove [180].”
BackgroundMontoya, J. J., Turnidge, M. A., Wai, D., Patel, A. R., Lee, D. W., Gokhale, V. M., Hurley, L. H., Arceci, R. J., Wetmore, C., & Azorsa, D. O. (2019) · BMC Cancer · doi:10.1186/s12885-019-6464-9 · Cited by 28 · see citing works
Srinivasan, S., Velu, R., DeRosa, M. C., & Murari, B. M. (2019) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-018-1484-x · Cited by 28 · see citing works
Farhath, M. M., Thompson, M. G., Ray, S., Sewell, A. L., Balci, H., & Basu, S. (2015) · Biochemistry · doi:10.1021/acs.biochem.5b00209 · Cited by 27 · see citing works
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G-quadruplex ligands mediate downregulation of DUX4 expression
Ciszewski, L., Lu‐Nguyen, N., Slater, A., Brennan, A., Williams, H. E. L., Dickson, G., Searle, M. S., & Popplewell, L. J. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa146 · Cited by 27 · see citing works
Fedeles, B. I. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1701244114 · Cited by 25 · cited 3× · see citing works
“G4-sequencing has further revealed that G4s are highly enriched in the promoters and TSSs of human and mouse genes [35].”
Background
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Deiana, M., Castán, J. M. A., Josse, P., Kahsay, A. G., Sánchez, D. P., Morice, K., Gillet, N., Ravindranath, R., Patel, A. K., Sengupta, P., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad365 · Cited by 66 · see citing works
“In addition, guanine has the lowest redox potential among the four DNA bases and runs of guanines render these sequences e v en more prone to oxidation ( 51 , 108 ) providing opportunities to maximize DNA damage by using G4-specific PSs.”
Epithelial–mesenchymal plasticity in kidney fibrosis
Hadpech, S., & Thongboonkerd, V. (2023) · genesis · doi:10.1002/dvg.23529 · Cited by 62 · see citing works
“ROS also acts as a secondary messenger in cellular signaling pathways (Ming et al., 2022; Wu et al., 2023).”
BackgroundG-quadruplexes and associated proteins in aging and Alzheimer’s disease
Kumar, M. J. V., Morales, R., & Tsvetkov, A. S. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1164057 · Cited by 34 · see citing works
“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).”
BackgroundMultifunctional Cerium Oxide Nanozyme for Synergistic Dry Eye Disease Therapy
Zou, H., Hong, Y., Xu, B., Wang, M., Xie, H., Wang, Y., & Lin, Q. (2024) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.4c07390 · Cited by 30 · see citing works
Luo, T., Yang, S., Zhao, T., Zhu, H., Chen, C., Shi, X., Chen, D., Wang, K., Jiang, K., Xu, D., et al. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05913-x · Cited by 28 · see citing works
Wang, Z., Zhou, J., Lin, L., & Hu, M.-H. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.116046 · Cited by 23 · see citing works
Moazamian, A., Saez, F., Drevet, J. R., Aitken, R. J., & Gharagozloo, P. (2025) · Antioxidants · doi:10.3390/antiox14050570 · Cited by 22 · see citing works
“When 8-OHdG is converted to an AP site within potential G4 sequences, these structural changes can further modify local methylation dynamics [97].”
Atiakshin, D., Kostin, A. A., Volodkin, A. V., Nazarova, A. A., Шишкина, В. В., Esaulenko, D., Buchwalow, I., Tiemann, M., & Noda, M. (2023) · Pharmaceuticals · doi:10.3390/ph16060817 · Cited by 20 · see citing works
G-quadruplex-mediated genomic instability drives SNVs in cancer
Richl, T., Kuper, J., & Kisker, C. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae098 · Cited by 20 · see citing works
“Furthermore, G4s are highly susceptible to oxidative damage, as G-rich sequences have a low redox-potential and thus can act as ROS-sinks ( 84 ).”
BackgroundLong, Y., Shi, H., Ye, J., & Qi, X. (2025) · Antioxidants · doi:10.3390/antiox14010114 · Cited by 22 · see citing works
Zhang, X., Wang, J., & Hu, M.-H. (2024) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.4c00234 · Cited by 19 · see citing works
Prasad, K., Sasi, S., Weerasinghe, J., Levchenko, I., & Bazaka, K. (2023) · Molecules · doi:10.3390/molecules28227481 · Cited by 19 · see citing works
“Hydroxyl radicals, on the other hand, cause direct damage to the DNA by oxidization of pyrimidine and purine bases leading to the formation of 8-hydroxy-2-deoxygunoise and other oxidative lesions, which then interfere with usual DNA replication and transcription [70].”
BackgroundCold plasma irradiation inhibits skin cancer via ferroptosis
Sun, T., Liu, C., Kong, L., Zha, J., & Ni, G. (2024) · Biomedical Physics & Engineering Express · doi:10.1088/2057-1976/ad8200 · Cited by 13 · see citing works
Metal nanozymes modulation of reactive oxygen species as promising strategies for cancer therapy
Bu, J.-W., Wang, Z., Liu, H., & Liu, S. (2024) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2024.124453 · Cited by 13 · see citing works
RNA–DNA Differences: Mechanisms, Oxidative Stress, Transcriptional Fidelity, and Health Implications
Štolc, V., Preto, O., Karhánek, M., Freund, F., Griko, Y. V., Loftus, D. J., & Ohayon, M. M. (2025) · Antioxidants · doi:10.3390/antiox14050544 · Cited by 12 · see citing works
Maurizio, I., Ruggiero, E., Zanin, I., Conflitti, M., Nicoletto, G., Provvedi, R., & Richter, S. N. (2025) · Nature Communications · doi:10.1038/s41467-025-62485-4 · Cited by 10 · see citing works
“ROS have been demonstrated to be responsible for the reduced thermal stability of G4s due to guanine oxidation and consequent disruption of the Hoogsteen hydrogen bonds 43,56 .”
Ye, H.-F., Zhang, H., Xiang, J., Shen, G., Yang, F., Wang, F., Wang, J., & Tang, Y.-L. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.127825 · Cited by 9 · see citing works
Comptdaer, T., Tardivel, M., Schirmer, C., Buée, L., & Galas, M. (2024) · Brain Pathology · doi:10.1111/bpa.13262 · Cited by 8 · see citing works
“This implies that robust prosurvival mechanisms are in place to prevent cell death during all this time [ 39, 42, 44].”
Causes and consequences of DNA double-stranded breaks in cardiovascular disease
Marian, A. J. (2024) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-024-05131-9 · Cited by 8 · see citing works
“In addition, oxidized bases and the abasic sites could affect DNA secondary structures, such as the G quadruplexes, and induce transcription stress [45].”
Valipour, M., Sheibani, M., Dibaei, M., Khatir, Z. Z., Ayati, A., Motafeghi, F. S., & Irannejad, H. (2025) · Drug Development Research · doi:10.1002/ddr.70071 · Cited by 8 · see citing works
“Furthermore, G ‐ quadruplexes are connected to oxidative stress, which can lead to DNA damage and promote genomic instability, a contributing factor in the onset of cancer (Stein and Eckert 2021; Stein and Eckert 2021; S. Wu et al. 2023).”
Reactive oxygen species-scavenging nanoantioxidants in inflammation: Design and therapy
Yan, J., Sun, F., Wang, M., & Wang, X. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.12.046 · Cited by 8 · see citing works
Mitochondrial dysfunction as the “mother” of all hallmarks of aging
Weissig, V. (2025) · Journal of Mitochondria Plastids and Endosymbiosis · doi:10.1080/28347056.2025.2560191 · Cited by 7 · see citing works
Wang, R., Wang, X.-D., & Hu, M.-H. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c02600 · Cited by 7 · see citing works
Zhang, X., & Hu, M.-H. (2024) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2024.136952 · Cited by 7 · see citing works
Apetroaei, M.-M., Baliou, S., Ιωάννου, Π., Fragkiadaki, P., Ștefan, G., Nedea, M. I., Burcea-Dragomiroiu, G.-T.-A., Velescu, B. Ș., Docea, A. O., Udeanu, D. I., et al. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47040273 · Cited by 6 · see citing works
“Proliferative signals are integrated with cell cycle checkpoints through the pRb-E2F pathway, which ensures correct cellular division and genomic stability [10].”
Yu, B., Zhang, W., Shao, Z., Chen, X., Cen, Y., Liu, Y., Chen, Y., Li, X., Liang, Z., Li, S., et al. (2025) · Chemical Science · doi:10.1039/d5sc01953b · Cited by 6 · see citing works
Stability of non-canonical nucleic acid structure as a potential modulator of cell fate
Takahashi, S., Tateishi‐Karimata, H., & Sugimoto, N. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf1486 · Cited by 8 · see citing works
“ROS also promotes the transcription of proto-oncogenes, such as BCL2 , KRAS , and c-Kit [ 242 ], suggesting that ROS can induce various types of cancer progression.”
Ou, J., Chen, Q., Wang, Y., Zhang, J., Wang, X., Wang, Q., Feng, Y., & Meng, X. (2024) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2024.137025 · Cited by 6 · see citing works
Mechanisms underlining R-loop biology and implications for human disease
Liu, J., Li, F., Cao, Y., Lv, Y., Lei, K., Tu, Z., Gong, C., Wang, H., Liu, F., & Huang, K. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1537731 · Cited by 6 · see citing works
“Reactive oxygen species (ROS) could also promote the production of R-loops through inducing the production of G4 structures in cells and could be further enhanced through G4 ligands (Wu et al., 2023).”
Wang, W., Li, S., Zhu, Y., Zhu, R., Du, X., Cui, X., Wang, H., & Zhou, C. (2024) · Foods · doi:10.3390/foods13030503 · Cited by 6 · see citing works
“The reactive oxygen species (ROS) produced during the metabolic process is one of the main causes of aging [15].”
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Unravelling the noncanonical extracellular DNA structures in biofilm and NETosis
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“The process of NETosis, driven by oxidative stress and chromatin decondensation, creates an environment that is conducive for the formation of structures like G4 and Z-DNA through the formation of 8-oxo-guanine (8-oxoG) [ 80 , 97 –99 ].”
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A bichromophoric squaraine based NIR fluorescent probe for G-quadruplex in living cells
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Protective effect of Pyripyropene A on H 2 O 2 -induced DNA oxidative damage in L02 cells
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Chromosomal Instability and Telomere Attrition in Systemic Sclerosis: A Historical Perspective
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Structural Insights into Spare-Tire DNA G-Quadruplex from the Human VEGF Promoter
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G-quadruplex DNA reprograms the photochemistry of CX-5461 toward radical-driven anticancer activity
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- Authors
- Wu, S., Jiang, L., Lei, L., Fu, C., Huang, J., Hu, Y., Dong, Y., Chen, J., & Zeng, Q.
- Affiliations
- Central South University (CN)
- Corresponding author
- Chen, Jing
- Zeng, Qinghai
- Venue
- Cell Death & Disease
- Published
- 2023-01-18
- Volume
- 14
- Issue
- 1
- Pages
- 37-37
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC9849334
- OpenAlex
- W4317234399
- Cited by
- 69
- References
- 229
- Citations by year
- 2026: 17 · 2025: 28 · 2024: 14 · 2023: 10
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82103704, 82073420, 82073421, No. 82103704, 82003326, YX202007)
- Central South University (YX202007)
- Xiangya Hospital, Central South University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Keywords
- G-quadruplex, reactive oxygen species, oxidative DNA damage, G-rich sequences, stress granules, Nrf2, aging, age-related diseases, transcriptional regulation, telomere maintenance, epigenetic regulation, redox potential
- MeSH terms
- DNA, Regulatory Sequences, Nucleic Acid, Reactive Oxygen Species, Epigenesis, Genetic, G-Quadruplexes
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