When we think of DNA, the first image that comes to mind is, of course, the double helix. Two strands winding around each other and stretching on and on have become the familiar symbol of DNA itself. But by now, we have seen that DNA is not limited to this iconic shape. Depending on the circumstances, it can bend and twist into other forms such as A-DNA and Z-DNA, and particular repetitive sequences can produce unusual protruding structures such as hairpins and cruciforms. Even so, all of these were still well-motivated transformations that took place within the basic framework of two DNA strands.
With the triplex, however, the story began to change. Things became more complicated—and much more unconventional. It was surprising enough to learn that a third strand can enter the major groove of an existing double helix and form Hoogsteen bonds, creating a three-stranded DNA structure. But DNA’s transformations do not stop there. This time, there are four strands. And it is not simply a matter of four strands lying side by side. Bases come together to form flat planes, these planes stack on top of one another, and entirely different three-dimensional structures can emerge depending on how the strands connect and fold. These four-stranded structures are found mainly in G-rich regions. And if one strand is rich in G, its complementary strand will naturally be rich in C. When the double helix opens, the G-rich strand can fold into a G-quadruplex, while the C-rich strand can form another unusual four-stranded structure called an i-motif. At this point, I almost feel a little sorry for having tried to define the appearance of DNA by the long, straight double helix I first imagined. DNA is not fixed in a single form. It is a remarkably dynamic molecule that folds and unfolds into shapes far beyond what we might expect, responding continuously to its surroundings.
Following our look at triple-helical DNA, this article will explore four-stranded structures. Compared with a triplex, where one additional strand joins a double helix, a four-stranded structure feels like a much more dramatic transformation. So, to find out why DNA takes on such strange-looking(?) forms and what they might mean, let us begin with the G-quadruplex, which forms in G-rich sequences.
G-quadruplex: a four-stranded nucleic acid structure
Another representative example of structural polymorphism created by a particular base sequence is the G-quadruplex, or G4 structure. The structural basis for G4 was recognized in the early 1960s, when it was shown that four G bases could form a flat G-quartet through Hoogsteen hydrogen bonding, and G4 structures were later detected in the nuclei of human cells in 2013. [1] In the DNA triplex we looked at in the previous article, the third strand targeted purine bases in the existing double helix through Hoogsteen bonding. If purine-rich repetitive regions were central to triplex formation, the key to G4 formation is a stretch of consecutive G bases. In a G-rich sequence known as a G-tract, four G bases can form eight Hoogsteen hydrogen bonds with one another instead of WC base pairs, creating a square, planar structure called a G-tetrad. Loops connect the G-tracts, while the resulting G-tetrads stack one above another to form a stable layered structure. This bookshelf-like stack of G-tetrads is the basic architecture of a G4.
For a G4, a non-canonical secondary structure formed in G-rich sequences, to remain stable, a monovalent cation is needed at the center of the structure. These cations coordinate with the partially negatively charged O6 oxygen atoms of G, reducing electrostatic repulsion among the oxygen atoms gathered in the center and helping prevent the tetrad stack from collapsing. Two representative monovalent cations available under physiological cellular conditions are potassium (K⁺) and sodium (Na⁺). Because its size and coordination properties fit the central channel of a G4 particularly well, K⁺ generally stabilizes G4 structures more strongly than Na⁺. In fact, the concentration of K⁺ inside cells is higher than that of Na⁺. On the other hand, even in the presence of these stabilizing ions, some divalent cations such as Mn²⁺, Co²⁺, or Ni²⁺ can, under certain conditions, destabilize or disrupt G4 structures. G4 has a higher-order geometry very different from that of the standard B-form DNA double helix. It can form naturally in single-stranded DNA or RNA, and in some cases several separate strands can participate in forming the structure.
G4 topology
One of the most striking features of G4 structures is the wide variety of topologies they can adopt. Put simply, topology describes the structural arrangement of the four strands—which direction they run in and how the loops connect them. G4 topologies are classified mainly according to strand orientation and the anti or syn orientation of the G bases. The topology of a G4 is influenced by many factors, including the number of consecutive G bases, loop length, the bases that make up the loops, the type of surrounding monovalent cation, and temperature. These conditions influence the directions adopted by the strands, and the orientations of the G bases adjust accordingly. DNA strands have an inherent 5′→3′ directionality. When all four strands run in the same direction, the G4 is parallel. When two strands run in one direction and the other two in the opposite direction, it is antiparallel. When three strands run in one direction and one runs in the opposite direction, a hybrid structure can form. The outward-facing anti orientation and the inward-folded syn orientation of G are closely related to strand direction. In an antiparallel G4, where strands run in opposite directions, some G bases must adopt the syn orientation. This is because an all-anti arrangement would not properly align the atoms needed for Hoogsteen bonding, so some G bases must flip into the syn orientation to bring the bonding atoms into the correct positions. As a result, parallel G4 structures tend to have grooves of similar width, whereas antiparallel structures contain a mixture of wider and narrower grooves. These differences in groove width can in turn influence where and how proteins interact with the G4 surface.
The loops connecting consecutive G-tracts can be classified as propeller, lateral, or diagonal according to strand orientation and the way the strands are connected. Propeller loops connect strands running in the same direction, lateral loops connect adjacent strands running in opposite directions, and diagonal loops connect strands positioned diagonally across from one another. Loop length and position are major factors in determining the overall G4 topology, and certain topologies can form only under particular loop-length conditions. Short loops, for example, tend to favor parallel structures, whereas longer loops can allow antiparallel arrangements. As a general tendency, K⁺ favors parallel structures, while Na⁺ can favor non-parallel structures including antiparallel forms, although the actual topology also depends on the sequence and loop conditions.
The remarkable diversity of G4 topologies
The image below shows that a G4 formed by a single DNA strand does not have just one possible shape. Depending on how the loops connect and the directions in which the strands run, it can adopt a remarkable variety of topologies. In other words, even when the same sequence and the same basic stacking of G-tetrads are involved, changing the positions and directions of the loops can produce entirely different structures. From these combinatorial possibilities, 26 standard G4 loop topologies are theoretically possible. Of these, 14 have so far been observed in high-resolution structural studies. [2] To understand why the remaining topologies are much less readily formed, this study computationally analyzed nearly 20,000 G4 structures generated from 128 DNA sequences. The results pointed to geometric constraints imposed by the loops as an important factor. In particular, folding became more difficult when a propeller loop had to connect G-tracts separated by a greater distance rather than nearby ones. So although the number of structures actually observed is more limited than the theoretical possibilities suggest, the diversity is still remarkable. Different topologies create different molecular surfaces, providing a wide range of binding interfaces through which different proteins can interact selectively with G4 structures. In addition, the presence of syn-oriented G bases creates differences in groove width, adding another layer of structural recognition beyond the underlying sequence and providing a basis for highly specific interactions with particular proteins.
Intramolecular vs intermolecular G4 structures
G4 structures can form not only intramolecularly, when a single nucleic-acid strand folds back on itself, but also intermolecularly, when two or four separate G-rich strands assemble together. In all of these cases, the basic principle is the same: four G-tracts come together to form G-tetrads. The difference lies in how those G-tracts are supplied by the participating strands, which allows several different modes of assembly. In an intermolecular G4, two independent strands can each contribute two G-tracts to form a bimolecular structure, or four independent strands can each contribute one G to a tetrad in a tetramolecular structure. Such structures tend to form more readily when single-stranded nucleic acids are sufficiently exposed and separate molecules have a higher chance of encountering one another—for example, at high concentrations, within confined spaces, or under particular ionic conditions.
Inside cells, DNA exists mainly as a double helix, so intermolecular G4 formation is relatively uncommon. It can nevertheless become possible when DNA is temporarily exposed as single strands during processes such as replication or transcription, or in environments containing G-rich RNAs. RNA is inherently single-stranded, so at high local concentrations inside the cell, intermolecular G4 formation between RNA molecules can be relatively more favorable.
Even so, from a functional point of view, most of the major biological roles of G4 structures in cells are associated with intramolecular G4s. Because an intramolecular G4 can form spontaneously within a single molecule, its formation is less dependent on concentration and faces fewer constraints than an intermolecular G4, which requires separate molecules to encounter one another. In artificial systems, however, external strands can be introduced to overcome these limitations or expand structural diversity. For example, a particular G-rich strand or a modified nucleic acid such as LNA or PNA can invade or bind an existing sequence and promote G4 formation, allowing hybrid G4 structures to be designed. Such hybrid structures appear only to a limited extent under natural conditions, but they can be useful tools for structural control and functional expansion in applications such as aptamer design and nanostructure engineering. In this sense, intramolecular G4s play a central role in biological systems because they can form stable, well-defined topologies, whereas intermolecular and hybrid G4s are generally more dynamic and condition-dependent. They may be more limited in nature, but in engineered systems they offer valuable ways to expand structural diversity and function.
A structural switch that regulates genome function
So why does DNA form such a complicated four-stranded structure that looks so different from standard B-DNA? G4 is not simply a structural deformation. It can act as a structural switch that helps regulate genome function. Genome-wide sequencing approaches have detected more than 700,000 G4-forming sites in the human genome, with these sites particularly enriched in regions such as gene promoters and telomeres. [3] Promoters, telomeres, and replication origins—the regions where G4 formation is frequently observed or predicted—are all central to genome function. For DNA replication or transcription to proceed, the double helix must open smoothly and expose single-stranded DNA. But if a G4 forms during this process and several planar G-tetrads stack together, the structure can quite literally become a physical obstacle, slowing DNA or RNA polymerase or even causing it to pause temporarily. This physical property allows G4 structures to act much like structural on-off switches for gene expression. Instead of regulation occurring only through the underlying sequence, the three-dimensional structure adopted by the DNA itself can influence gene expression, making G4 a representative example of structure-based regulation.
Helicases that unwind G4 structures
Cells can form G4 structures when conditions favor them, but when replication or transcription must proceed smoothly, these structures also need to be removed so that DNA can return to the standard B-form. Cells therefore contain helicases capable of recognizing and unwinding G4 structures. Representative examples include DHX36 (RHAU), WRN, BLM, and FANCJ, which use energy from ATP to dismantle G4 structures. If we were to compare the way these helicases work to something familiar, it would be less like straightening curly hair all at once with a flat iron and more like patiently loosening a tangled knot, one strand—or one layer—at a time.
Biological functions of G4
G4 structures, then, are not simply abnormal structures that interfere with replication and transcription. They can also be viewed as important structural elements involved in regulating genome function. Their major biological roles can be broadly summarized in three ways.
First, G4 structures can regulate transcription. G4-forming sequences are found in the promoters of several oncogenes, including MYC, KRAS, and BCL2. When a G4 forms in such a region, it can physically restrict access by RNA polymerase and transcription factors, thereby suppressing transcription. Unlike regulation in which a particular protein reads a DNA sequence, this is an example in which the structure formed by the DNA itself can act as a transcriptional regulatory signal.
Second, G4 structures are involved in regulating DNA replication. They are found relatively frequently around replication origins and are thought to participate in controlling the timing of replication initiation and the rate at which replication forks progress. If a G4 forms transiently as the DNA strands open during replication, it can alter the speed of fork progression, potentially contributing to fine control of replication timing.
Third, G4 structures contribute to telomere stability. Telomeres consist of repeated TTAGGG sequences and are therefore highly G-rich, making G4 formation particularly favorable. G4 structures formed at telomeres can regulate access by telomerase and reduce excessive exposure of chromosome ends, contributing to the maintenance of telomere stability.
Telomere protection mechanisms and G4
We often say that “telomeres protect the ends of chromosomes,” but interestingly, what they are protecting those ends from is largely the cell’s own DNA damage-sensing and repair systems. When an exposed DNA end is detected, the cell can mistake it for a double-strand break and activate a repair response. One possible result is end-to-end fusion, in which the ends of different chromosomes become joined together.
Telomeres use several structural mechanisms to prevent this mistaken response. First, histone modifications and protein binding help establish a heterochromatin-like state at telomeric regions. This tightly packed and condensed chromatin makes the region less accessible to proteins and helps keep the DNA end from becoming easily exposed. In this sense, the compact structure itself acts as part of the protective system.
Telomere ends also contain a single-stranded 3′ overhang, which folds back into the double-stranded region to form a T-loop. This physically hides the single-stranded end. In addition, the shelterin protein complex binds to telomeres and suppresses DNA damage responses, preventing DNA repair systems from recognizing telomeres as broken DNA ends. The G-rich telomeric sequence can also form G4 structures, reducing exposure of the single-stranded end and physically limiting access by various enzymes. Together, these protective mechanisms allow telomeres to shield chromosome ends and help preserve genome integrity.
Cancer cells and G4 stabilization
Cells regulate gene expression and DNA replication in part by forming and resolving G4 structures as needed. When replication or transcription needs to proceed, helicases capable of unwinding G4 use ATP to dismantle the structure, allowing the DNA to form a double helix again. G4 structures also need to be resolved when telomerase must extend a telomere.
Problems arise, however, when this regulation does not work properly. If G4 structures become excessively stabilized or are not resolved at the appropriate time, replication can be obstructed and DNA damage can accumulate. In particular, when a replication fork encounters a G4 structure, the fork can stall or collapse, potentially causing severe DNA damage such as double-strand breaks. If such damage accumulates repeatedly, genome instability increases, which is closely associated with cancer development. This kind of problem is indeed observed when helicases involved in resolving G4 structures are defective. Mutations or defects in the WRN, BLM, and FANCJ helicase genes, for example, cause Werner syndrome, Bloom syndrome, and Fanconi anemia, respectively. These disorders share features of increased genome instability and an elevated risk of cancer. [4]
RNA helicases, which dynamically regulate RNA structure by unwinding or rearranging RNA secondary and tertiary structures, are also closely connected with diseases involving G-rich repetitive sequences. The C9ORF72 gene contains GGGGCC repeats, and when these repeats expand abnormally, excessive G4 structures can form at the RNA level. Such expanded repeat RNAs can adopt several secondary structures, including G4s, and RNA helicases participate in resolving these structures and regulating RNA metabolism. Abnormalities involving the repeat RNA and the RNA-processing environment around it are thought to contribute through several pathways—including abnormal translation and the production of toxic proteins—to the mechanisms underlying neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). [5]
G4 structures as targets for anticancer therapy
Although G4 structures can contribute to conditions that increase cancer risk, they may also play an important role in strategies designed to target cancer cells. Many oncogene promoters contain G-rich sequences capable of forming G4 structures. G4 formation has been demonstrated in the promoters of major oncogenes such as MYC, KRAS, and BCL2, and stabilizing G4 at these sites can interfere with access by RNA polymerase and suppress transcription. This means that compounds capable of selectively stabilizing G4 structures could potentially be used to suppress oncogene expression.
G4 structures are also important at telomeres. Telomeric sequences readily form G4 structures, and in vitro experiments have shown that G4 formation can inhibit telomere extension by telomerase. [6] In most normal somatic cells, telomerase activity is generally switched off. If cells were able to divide indefinitely, mutations could continue to accumulate, greatly increasing the risk of cancer. For this reason, telomerase activity has been evolutionarily suppressed in many somatic cells as part of a broader barrier against unlimited proliferation. Cancer cells, however, can reactivate telomerase through several mechanisms, allowing them to acquire the ability to divide indefinitely and continue proliferating.
As we saw above, G4 structures can act as a natural structural brake by restricting the access of enzymes, including telomerase. For this reason, stabilizing G4 structures is being actively investigated as a potential way to suppress the proliferation of cancer cells. In 2024, imetelstat, an oligonucleotide drug that directly inhibits telomerase, was approved by the U.S. FDA for certain patients with low- or intermediate-1-risk myelodysplastic syndromes (MDS). [7] Telomerase inhibition, however, can take time to produce an effect, and some cancer cells can maintain their telomeres through mechanisms that do not depend on telomerase. As a result, telomerase inhibition alone may not always produce a sufficient antitumor effect, and combination strategies with other anticancer approaches are also being investigated.
G4 is not simply an unusual non-canonical structure that DNA happens to form by chance. It can be viewed as a representative example of structure-based regulation, in which the shape of DNA itself influences gene function. Higher-order non-canonical structures such as G4 can physically obstruct the access or progression of polymerases and can act as regulators through the structure itself. In other words, independently of proteins that read the underlying sequence, the formation of a G4 can itself influence polymerase progression and protein binding. Ultimately, gene regulation can depend not only on the base sequence but also on the structure adopted by the DNA. And if a G4 forms in a G-rich sequence, the complementary strand will naturally contain a C-rich sequence. Under the right conditions, this C-rich strand can form another higher-order non-canonical DNA structure known as the i-motif.
i-motif structure
Just as G-rich sequences can form G4 structures, C-rich sequences can form another unusual non-canonical DNA structure known as the i-motif, short for intercalated motif. C-rich sequences provide the basic foundation for i-motif formation. Although the structure was first proposed in 1993, for many years it was regarded mainly as an artificial structure that formed only in vitro. That view changed in 2018, when i-motif structures were directly observed in the nuclei of living human cells, confirming that they can also form inside cells and leading to a rapid expansion of research in this area. [1]
The principle behind i-motif formation is completely different from that of G4. In a G4, four G bases form Hoogsteen hydrogen bonds to create a flat G-tetrad, and these tetrads stack on top of one another. In an i-motif, by contrast, one of two C bases becomes protonated and forms a distinctive hydrogen-bonded C–C⁺ base pair. These C–C⁺ pairs then intercalate with one another, fitting together in an alternating fashion so that the DNA strands interlock almost like a zipper. This intercalated arrangement is what gives the structure its name: the intercalated motif, or i-motif.
The i-motif was first reported as an intermolecular structure formed under acidic conditions from DNA sequences such as d(TCCCCC). (Here, the “d” indicates a DNA sequence composed of deoxyribonucleotides, distinguishing it from RNA.) The i-motif is stabilized by C·C⁺ base pairs in which one of the two C bases is protonated. Because only one of the two cytosines carries the additional proton, this is called hemi-protonation. Based on these C–C⁺ interactions, two parallel duplex-like units intercalate with one another in opposite directions, producing an overall four-stranded structure.
This structure is particularly stable under mildly acidic conditions. As we saw earlier when looking at triplex formation, C must accept a proton (H⁺) and become C⁺ for a stable C–C⁺ base pair to form. For this reason, i-motifs were long thought to be difficult to form in the near-neutral pH environment inside cells. More recent studies, however, have shown that i-motif structures can indeed form in cells under conditions involving transient local pH changes, DNA supercoiling, exposure of single-stranded DNA, and protein binding.
i-motif topology
An i-motif can form intramolecularly when a single strand folds back on itself, or intermolecularly when two or four separate strands come together. Different structural forms become possible depending on the number of C bases, solution conditions, and loop length. In addition, i-motifs can be classified by their intercalation topology according to whether the outermost exposed C–C⁺ base pair lies at the 3′ or 5′ end. These arrangements are called 3′-end exposed (3′E) and 5′-end exposed (5′E), respectively. In general, the 3′E topology is known to be relatively more stable because of sugar–sugar interactions formed along the narrow groove. [8]
Relationship between G4 and i-motif structures
One particularly interesting feature of the i-motif is that the places where it forms are closely related to sites capable of forming G4 structures. Because the strand complementary to a G-rich G4-forming sequence is naturally C-rich, the two structures can potentially form on opposite strands at the same DNA region. G4s and i-motifs also share several features. Both are frequently found in gene promoter regions and have been identified in genes such as MYC, BCL2, KRAS, and VEGF. Both are also highly dynamic structures, repeatedly folding, unfolding, and folding again.
Cells can form or resolve these structures as conditions change, and when replication or transcription needs to proceed, various helicases and binding proteins can act to dismantle them. Most importantly, both G4 and i-motif structures can influence access by RNA polymerase and transcription factors through the physical shape of the DNA itself, allowing them to participate in the regulation of gene expression.
The fact that G4 and i-motif structures can form within the same DNA region also raises the possibility that their formation can influence one another and, in some situations, compete with one another. This dynamic interplay itself may function as a structural switch involved in regulating gene expression.
More recently, genomic regions in which G4 and i-motif structures can both form have attracted attention as potential targets for anticancer therapy. One reason is that stabilizing these structures with particular compounds can, in some cases, suppress transcription at oncogene promoters. Compared with G4-targeting approaches, however, research on drugs that specifically target i-motifs is still at an early stage, and considerably more work will be needed before such approaches become established therapeutic strategies.
From this perspective, G4 and i-motif structures are more than simply unusual non-canonical DNA structures. They can be viewed as examples of a structure-based information system in which DNA uses its own shape to influence gene function. In other words, the genome carries not only information in its base sequence but also another layer of information in the structures that DNA can adopt, and this structural layer can help regulate a wide range of biological processes.
Image 8. Various non-canonical DNA structures: triplex DNA, G4, i-motif, hairpin, cruciform, and R-loop
We have now looked beyond standard B-DNA at several non-canonical structures, including triplex DNA, G4 structures, and i-motifs. When I began this article, the question I had was simple: why on earth does DNA make such strange shapes? Looking back over what we have seen, these structures do not seem to be merely odd shapes that DNA happens to form by accident. Under the right conditions, particular sequences can fold into alternative structures according to their own physicochemical properties. Once the structure changes, it may slow or block the path of a polymerase, or create a new three-dimensional surface to which proteins can bind. And if such changes occur at important sites such as promoters, replication origins, or telomeres, they can influence transcription, replication, and chromosome-end function.
G4 and i-motif structures can also form and disappear in response to factors such as the ionic environment, temporary exposure of single-stranded DNA, supercoiling, and surrounding proteins. From this point of view, a change in DNA structure may be more than simply a change in shape. It may serve as a kind of structural switch—and perhaps, in some situations, even something like a sensor—that responds to changes in the local environment and connects them to genome function.
Thinking about all this leads me to another possibility. If an existing DNA sequence can fold and unfold according to the conditions around it, becoming a physical barrier or a binding signal in its own right, might that be a rather efficient way for a cell to respond to change instead of having to produce a new regulatory protein every time? Compared with synthesizing a new protein, perhaps it could require less energy and allow a faster response.
This is still my own line of reasoning as I write, but after looking at G4s and i-motifs, it has become difficult for me to think of DNA as nothing more than a static molecule that stores information in a base sequence. Alongside the information contained in which bases are arranged where, there is another structural possibility hidden in the sequence itself: under what conditions, and into what shapes, that sequence can fold. Cells do in fact connect the formation and resolution of these structures with transcription, replication, and telomere regulation. In the end, DNA is not a molecule that simply sits still while storing genetic information. It is a far more dynamic molecule, constantly folding and unfolding as it interacts with the molecules and environment around it.
[References]
[1] Insights into the Molecular Structure, Stability, and Biological Significance of Non-Canonical DNA Forms, with a Focus on G-Quadruplexes and i-Motifshttps://doi.org/10.3390/molecules29194683
[2] Large-Scale Conformational Analysis Explains G-Quadruplex Topological Landscape
https://doi.org/10.1021/acs.jpcb.5c04372
[3] Long-range DNA interactions: inter-molecular G-quadruplexes and their potential biological relevance
https://doi.org/10.1039/d2cc04872h
[4] Non-canonical DNA structures: Diversity and disease association
https://doi.org/10.3389/fgene.2022.959258
[5] RNA Helicases in Microsatellite Repeat Expansion Disorders and Neurodegeneration
https://doi.org/10.3389/fgene.2022.886563
[6] Telomeres expand sphere of influence: emerging molecular impact of telomeres in non-telomeric functions
https://www.cell.com/trends/genetics/fulltext/S0168-9525%2822%2900250-5
[7] FDA approves imetelstat for low- to intermediate-1 risk myelodysplastic syndromes with transfusion-dependent anemia
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-imetelstat-low-intermediate-1-risk-myelodysplastic-syndromes-transfusion-dependent
[8] Advances in i-motif structures: Stability, gene expression, and therapeutic applications
https://doi.org/10.1016/j.ijbiomac.2025.143555
[Image sources]
Image 1
1-1. Telomeres expand sphere of influence: emerging molecular impact of telomeres in non-telomeric functions — CC BY-NC-ND 4.0
1-2. Non-B DNA: a major contributor to small- and large-scale variation in nucleotide substitution frequencies across the genome — CC BY-NC 4.0
Image 2
2-1. Beyond small molecules: targeting G-quadruplex structures with oligonucleotides and their analogues — CC BY 4.0
Image 3
3-1. Large-Scale Conformational Analysis Explains G-Quadruplex Topological Landscape — CC BY 4.0
Image 4
4-1. Recent Progress of Targeted G-Quadruplex-Preferred Ligands Toward Cancer Therapy — CC BY 4.0
4-2. Perspectives for Applying G-Quadruplex Structures in Neurobiology and Neuropharmacology — CC BY 4.0
Image 5
5-1. i-Motif DNA: structural features and significance to cell biology — CC BY-NC 4.0
5-2. Insights into the Molecular Structure, Stability, and Biological Significance of Non-Canonical DNA Forms, with a Focus on G-Quadruplexes and i-Motifs — CC BY 4.0
Image 6
6-1. i-Motif DNA: structural features and significance to cell biology — CC BY-NC 4.0
6-2. Insights into the Molecular Structure, Stability, and Biological Significance of Non-Canonical DNA Forms, with a Focus on G-Quadruplexes and i-Motifs — CC BY 4.0
Image 7
7-1. Major Achievements in the Design of Quadruplex-Interactive Small Molecules — CC BY 4.0
Image 8
8-1. In vivo detection of DNA secondary structures using Permanganate/S1 Footprinting with Direct Adapter Ligation and Sequencing (PDAL-Seq) — CC BY-NC-ND 4.0
1-2. Non-B DNA: a major contributor to small- and large-scale variation in nucleotide substitution frequencies across the genome — CC BY-NC 4.0
Image 2
2-1. Beyond small molecules: targeting G-quadruplex structures with oligonucleotides and their analogues — CC BY 4.0
Image 3
3-1. Large-Scale Conformational Analysis Explains G-Quadruplex Topological Landscape — CC BY 4.0
Image 4
4-1. Recent Progress of Targeted G-Quadruplex-Preferred Ligands Toward Cancer Therapy — CC BY 4.0
4-2. Perspectives for Applying G-Quadruplex Structures in Neurobiology and Neuropharmacology — CC BY 4.0
Image 5
5-1. i-Motif DNA: structural features and significance to cell biology — CC BY-NC 4.0
5-2. Insights into the Molecular Structure, Stability, and Biological Significance of Non-Canonical DNA Forms, with a Focus on G-Quadruplexes and i-Motifs — CC BY 4.0
Image 6
6-1. i-Motif DNA: structural features and significance to cell biology — CC BY-NC 4.0
6-2. Insights into the Molecular Structure, Stability, and Biological Significance of Non-Canonical DNA Forms, with a Focus on G-Quadruplexes and i-Motifs — CC BY 4.0
Image 7
7-1. Major Achievements in the Design of Quadruplex-Interactive Small Molecules — CC BY 4.0
Image 8
8-1. In vivo detection of DNA secondary structures using Permanganate/S1 Footprinting with Direct Adapter Ligation and Sequencing (PDAL-Seq) — CC BY-NC-ND 4.0
: G-Quadruplex (G4) and i-Motif Structures){kind=link}