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

Zhang, Jianye; Gao, Yue; Pan, Weifei; Yang, Yayuan; Li, Xu; Chen, Lingfei; Wang, Chang; Wang, Yuqing

doi:10.3389/fphar.2023.1136251

Cited by 7 publications

(3 citation statements)

References 169 publications

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“…Owing to their distinctive physicochemical properties, these i-motif structures have garnered considerable attention as novel targets for drug development (reviewed in ref. [ 80 ]); however, a thorough discussion of these secondary structures is beyond the scope of this review. Another factor that ties G4 folding to polymerase activity is the increased stability of the tetraplex in nanocages mimicking the confined space in the exit channel of polymerases [ 81 ].…”

Section: Overview Of the G-quadruplexmentioning

confidence: 99%

Spotlight on G-Quadruplexes: From Structure and Modulation to Physiological and Pathological Roles

Dell’Oca,

Quadri,

Bernini

et al. 2024

IJMS

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G-quadruplexes or G4s are non-canonical secondary structures of nucleic acids characterized by guanines arranged in stacked tetraplex arrays. Decades of research into these peculiar assemblies of DNA and RNA, fueled by the development and optimization of a vast array of techniques and assays, has resulted in a large amount of information regarding their structure, stability, localization, and biological significance in native systems. A plethora of articles have reported the roles of G-quadruplexes in multiple pathways across several species, ranging from gene expression regulation to RNA biogenesis and trafficking, DNA replication, and genome maintenance. Crucially, a large amount of experimental evidence has highlighted the roles of G-quadruplexes in cancer biology and other pathologies, pointing at these structurally unique guanine assemblies as amenable drug targets. Given the rapid expansion of this field of research, this review aims at summarizing all the relevant aspects of G-quadruplex biology by combining and discussing results from seminal works as well as more recent and cutting-edge experimental evidence. Additionally, the most common methodologies used to study G4s are presented to aid the reader in critically interpreting and integrating experimental data.

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Section: Overview Of the G-quadruplexmentioning

confidence: 99%

Spotlight on G-Quadruplexes: From Structure and Modulation to Physiological and Pathological Roles

Dell’Oca,

Quadri,

Bernini

et al. 2024

IJMS

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show abstract

“…These structures, which can be formed even at higher pH than the cytosine pK

(∼ 4.2 [ 5 ]), have recently been shown to also be present at physiological pH [ 6 , 7 ] and to also exist in vivo [ 8 , 9 ]—in regulatory regions of the human genome [ 9 ]. I-motifs have, thus, drawn a lot of attention for their involvement in cellular processes [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ] and, consequently, as targets for medical applications [ 17 , 18 , 19 ]. Moreover, they show promising potential in the fields of nanotechnology, biosensing and bioanalytics, which exploit their dependence on the pH of the embedding medium [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Shedding Light on the Photophysics and Photochemistry of I-Motifs Using Quantum Mechanical Calculations

Improta

2023

IJMS

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I-motifs are non-canonical DNA structures formed by intercalated hemiprotonated (CH·C)+ pairs, i.e., formed by a cytosine (C) and a protonated cytosine (CH+), which are currently drawing great attention due to their biological relevance and promising nanotechnological properties. It is important to characterize the processes occurring in I-motifs following irradiation by UV light because they can lead to harmful consequences for genetic code and because optical spectroscopies are the most-used tools to characterize I-motifs. By using time-dependent DFT calculations, we here provide the first comprehensive picture of the photoactivated behavior of the (CH·C)+ core of I-motifs, from absorption to emission, while also considering the possible photochemical reactions. We reproduce and assign their spectral signatures, i.e., infrared, absorption, fluorescence and circular dichroism spectra, disentangling the underlying chemical–physical effects. We show that the main photophysical paths involve C and CH+ bases on adjacent steps and, using this basis, interpret the available time-resolved spectra. We propose that a photodimerization reaction can occur on an excited state with strong C→CH+ charge transfer character and examine some of the possible photoproducts. Based on the results reported, some future perspectives for the study of I-motifs are discussed.

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“…Note that in addition to G4 sequences, on the complementary strand of G-quadruplexes, C-rich sequences can also form a four-stranded motif called an i-motif [ 19 , 20 ]. In this motif, cytosines form two interdigitated C•C + base-paired strands at a low pH [ 21 ], as shown in human telomere repeats and several oncogene promoters.…”

Section: Introductionmentioning

confidence: 99%

Genomic Instability of G-Quadruplex Sequences in Escherichia coli: Roles of DinG, RecG, and RecQ Helicases

Parekh,

Węgrzyn,

Arluison

et al. 2023

Genes

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Guanine-rich DNA can fold into highly stable four-stranded DNA structures called G-quadruplexes (G4). Originally identified in sequences from telomeres and oncogene promoters, they can alter DNA metabolism. Indeed, G4-forming sequences represent obstacles for the DNA polymerase, with important consequences for cell life as they may lead to genomic instability. To understand their role in bacterial genomic instability, different G-quadruplex-forming repeats were cloned into an Escherichia coli genetic system that reports frameshifts and complete or partial deletions of the repeat when the G-tract comprises either the leading or lagging template strand during replication. These repeats formed stable G-quadruplexes in single-stranded DNA but not naturally supercoiled double-stranded DNA. Nevertheless, transcription promoted G-quadruplex formation in the resulting R-loop for (G3T)4 and (G3T)8 repeats. Depending on genetic background and sequence propensity for structure formation, mutation rates varied by five orders of magnitude. Furthermore, while in vitro approaches have shown that bacterial helicases can resolve G4, it is still unclear whether G4 unwinding is important in vivo. Here, we show that a mutation in recG decreased mutation rates, while deficiencies in the structure-specific helicases DinG and RecQ increased mutation rates. These results suggest that G-quadruplex formation promotes genetic instability in bacteria and that helicases play an important role in controlling this process in vivo.

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

Cited by 7 publications

References 169 publications

Spotlight on G-Quadruplexes: From Structure and Modulation to Physiological and Pathological Roles

Spotlight on G-Quadruplexes: From Structure and Modulation to Physiological and Pathological Roles

Shedding Light on the Photophysics and Photochemistry of I-Motifs Using Quantum Mechanical Calculations

Genomic Instability of G-Quadruplex Sequences in Escherichia coli: Roles of DinG, RecG, and RecQ Helicases

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