Figure 1
Sequence and overall structure of DNA1. (A) Detailed sequence of DNA1. (B) Overall structure of DNA1 quadruplex. The DNAs are shown as cartoon-and-ring mode with the four strands colored in cyan, orange, green and red, respectively. The ions are shown as spheres; Li + , NH 4 + , Na + and Pb 2+ are colored in cyan, blue, yellow and black, respectively. (C) A schematic view showing the glycosidic assignments of each individual nucleotides. s and a refer to the syn and anti conformation around the glycosol bond, respectively.
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DNA can form diverse structures, which predefine their physiological functions. Besides duplexes that carry the genetic information, quadruplexes are the most well-studied DNA structures. In addition to their important roles in recombination, replication, transcription and translation, DNA quadruplexes have also been applied as diagnostic aptamers...
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... we further expand the structure and sequence complexity of DNA four-stranded architecture by pre- senting a high-resolution crystal structure of DNA1 (5 - AGAGAGATGGGTGCGTT-3 ). This is the first DNA structure that contains all the internal A-, G-, C-, T-tetrads, A:T:A:T tetrads, bulged nucleotides and multiple metal ions including Li + , NH 4 + , Na + and Pb 2+ in one single struc- ture (Figure 1). The central residues form one unique kink and 13 stacking tetrads, which are the longest tetrad layers formed within one quadruplex available to date. ...
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... crystal belongs to P2 1 2 1 2 space group, it con-tains two DNA1 molecules per asymmetric unit. Via the 2-fold symmetry along the long axis, DNA1 can assemble into quadruplex with four DNA strands parallelly orien- tated ( Figure 1). DNA1 is 17 nt long in length; whereas, there are more than 300 ordered water molecules observed in the DNA1 quadruplex structure ( Supplementary Fig- ure S1). ...
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... the 2-fold symmetry along the long axis, DNA1 can assemble into quadruplex with four DNA strands parallelly orien- tated ( Figure 1). DNA1 is 17 nt long in length; whereas, there are more than 300 ordered water molecules observed in the DNA1 quadruplex structure ( Supplementary Fig- ure S1). These water molecules are mainly located within the grooves and along the phosphate backbone of the quadruplexes; the extensive hydrogen bond (H-bond) in- teractions between the nucleotides and the water molecules may play important role in the folding and stabilization of the quadruplexes. ...
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... residues adopt syn-conformation in the A1:T17*:A1:T17* tetrad ( Figures 1C and 2F), which is different from the one in the A1:T16*:A1:T16* tetrad. In addition, it is also noteworthy that the sugar pucker conformation of the A1 residues is also different in the two tetrads, adopting C2 -endo and C2 -exo pucker respec- tively in A1:T16*:A1:T16* and A1:T17*:A1:T17* tetrads (Supplementary Figure S3B). ...
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... we further expand the structure and sequence complexity of DNA four-stranded architecture by pre- senting a high-resolution crystal structure of DNA1 (5 - AGAGAGATGGGTGCGTT-3 ). This is the first DNA structure that contains all the internal A-, G-, C-, T-tetrads, A:T:A:T tetrads, bulged nucleotides and multiple metal ions including Li + , NH 4 + , Na + and Pb 2+ in one single struc- ture (Figure 1). The central residues form one unique kink and 13 stacking tetrads, which are the longest tetrad layers formed within one quadruplex available to date. ...
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... crystal belongs to P2 1 2 1 2 space group, it con-tains two DNA1 molecules per asymmetric unit. Via the 2-fold symmetry along the long axis, DNA1 can assemble into quadruplex with four DNA strands parallelly orien- tated ( Figure 1). DNA1 is 17 nt long in length; whereas, there are more than 300 ordered water molecules observed in the DNA1 quadruplex structure ( Supplementary Fig- ure S1). ...
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... the 2-fold symmetry along the long axis, DNA1 can assemble into quadruplex with four DNA strands parallelly orien- tated ( Figure 1). DNA1 is 17 nt long in length; whereas, there are more than 300 ordered water molecules observed in the DNA1 quadruplex structure ( Supplementary Fig- ure S1). These water molecules are mainly located within the grooves and along the phosphate backbone of the quadruplexes; the extensive hydrogen bond (H-bond) in- teractions between the nucleotides and the water molecules may play important role in the folding and stabilization of the quadruplexes. ...
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... residues adopt syn-conformation in the A1:T17*:A1:T17* tetrad ( Figures 1C and 2F), which is different from the one in the A1:T16*:A1:T16* tetrad. In addition, it is also noteworthy that the sugar pucker conformation of the A1 residues is also different in the two tetrads, adopting C2 -endo and C2 -exo pucker respec- tively in A1:T16*:A1:T16* and A1:T17*:A1:T17* tetrads (Supplementary Figure S3B). ...
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In human cells, thymidylate synthase (TS) provides the only source of 2’-deoxythymidyne-5’-monophosphate (dTMP), which is required for DNA biosynthesis. Because of its pivotal role, human TS (hTS) represents a validated target for anticancer chemotherapy. Nonetheless, the efficacy of drugs blocking the hTS active site has limitations due to the ons...
Citations
... Among the 49 folds, 23, 13, and 13 are continuous, discontinuous, and higher-order folds. Although these folds are predominantly formed by G-quartets (Figure 1A), non-Gquartets like T-T-T-T (PDB ID: 7D31) [72,73], C-C-C-C (PDB ID: 6A85) [73], A-T-A-T (PDB ID: 5LS8) [74], G-C-G-C (PDB ID: 7CV4) [75], C-A-G-A (PDB ID: 6ZX7) [76], and G-G-A-T (PDB ID: 5VHE) [77] are also found. Out of the 223 sequences considered for the analysis, the number of sequences preferring continuous parallel folds (three folds) is more compared to the antiparallel and hybrid folds, viz., 81 unique sequences among 143 structures prefer parallel fold. ...
... Among the 49 folds, 23, 13, and 13 are continuous, discontinuous, and higher-order folds. Although these folds are predominantly formed by G-quartets (Figure 1A), non-Gquartets like T-T-T-T (PDB ID: 7D31) [72,73], C-C-C-C (PDB ID: 6A85) [73], A-T-A-T (PDB ID: 5LS8) [74], G-C-G-C (PDB ID: 7CV4) [75], C-A-G-A (PDB ID: 6ZX7) [76], and G-G-A-T (PDB ID: 5VHE) [77] are also found. Out of the 223 sequences considered for the analysis, the number of sequences preferring continuous parallel folds (three folds) is more compared to the antiparallel and hybrid folds, viz., 81 unique sequences among 143 structures prefer parallel fold. ...
DNA quadruplexes take part in many biological functions. It takes up a variety of folds based on the sequence and environment. Here, a meticulous analysis of experimentally determined 392 quadruplex structures (388 PDB IDs) deposited in PDB is carried out. The analysis reveals the modular representation of the quadruplex folds. 48 unique quadruplex motifs (whose diversity arises out of the propeller, bulge, diagonal, and lateral loops that connect the quartets) are identified, leading to simple to complex inter-/intra-molecular quadruplex folds. These structural two-layered motifs are further classified into 33 continuous and 15 discontinuous motifs. The discontinuous motifs cannot further be classified into parallel, antiparallel, or hybrid as one or more guanines of the adjacent quartets are not connected. While the continuous motifs can be extended to a quadruplex fold, the discontinuous motif requires additional loop(s) to complete a fold, as illustrated here with examples. Similarly, the higher-order quadruplex folds can also be represented by continuous or discontinuous motifs or their combinations. Such a modular representation of the quadruplex folds may assist in custom engineering of quadruplexes, designing motif-based drugs, and the prediction of quadruplex structure. Further, it could facilitate understanding the role of quadruplexes in biological functions and diseases.
... That formaldehyde is a passive DNA denaturing agent [34,35] entails that protein unbound G4s would be underrepresented in the G4-ChIP. In addition, tetrads formed by non-G nucleotides also exist interspersed between G tetrads, with some even stabilizing the G4s to varying degrees [36][37][38][39]. Currently, we do not know if the large fraction of DNA pulled down by antibodies specific for G4s that does not show any (G 3 -N (1)(2)(3)(4)(5)(6)(7) )xn signature is an artifact or not. ...
Our understanding of DNA G-quadruplexes (G4s) from in vitro studies has been complemented by genome-wide G4 landscapes from cultured cells. Conventionally, the formation of G4s is accepted to depend on G-repeats such that they form tetrads. However, genome-wide G4s characterized through high-throughput sequencing suggest that these structures form at a large number of regions with no such canonical G4-forming signatures. Many G4-binding proteins have been described with no evidence for any protein that binds to and stabilizes G4s. It remains unknown what fraction of G4s formed in human cells are protein-bound. The G4-chromatin immunoprecipitation (G4-ChIP) method hitherto employed to describe G4 landscapes preferentially reports G4s that get crosslinked to proteins in their proximity. Our current understanding of the G4 landscape is biased against representation of G4s which escape crosslinking as they are not stabilized by protein-binding and presumably transient. We report a protocol that captures G4s from the cells efficiently without any bias as well as eliminates the detection of G4s formed artifactually on crosslinked sheared chromatin post-fixation. We discover that G4s form sparingly at SINEs. An application of this method shows that depletion of a repeat-binding protein CGGBP1 enhances net G4 capture at CGGBP1-dependent CTCF-binding sites and regions of sharp interstrand G/C-skew transitions. Thus, we present an improved method for G4 landscape determination and by applying it we show that sequence property-specific constraints of the nuclear environment mitigate G4 formation.
... The most widely accepted DNA structure is the classical B-DNA form, which is a right-handed double helix in nature and contains the hydrogen bonds between the nucleobases as described by Watson andCrick in 1953 (Watson andCrick, 1953). Yet, it is evident that DNA is structurally dynamic and can also adopt alternative secondary structures like guanine-rich tetrads (Gellert et al., 1962) and non-guanine rich tetrads (Liu et al., 2018). Guaninerich DNA strands are capable of folding into four-stranded helical structures, called G-quadruplexes (G4s). ...
... It incorporates cG/cC and G4 hunter algorithms to evaluate better results. The continuous progress in literature providing evidence on the in-vitro existence of G4 structures containing more than four G-tracts (Phan et al., 2005;Omaga et al., 2018) and G4 structures containing all the possible tetrads, A:T:A:T tetrads and bulged nucleotides in one single structure (Liu et al., 2018) still remained to be incorporated into the search algorithm. Anotpther interesting role of G4 structures is to influence the methylation at CpG islands (CGIs), which are guaninecytosine-rich regions and are usually hypomethylated. ...
G-quadruplexes (G4s) are secondary structures in DNA that have been shown to be involved in gene regulation. They play a vital role in the cellular processes and several pathogens including bacteria, fungi, and viruses have also been shown to possess G4s that help them in their pathogenesis. Additionally, cross-talk among the CpG islands and G4s has been shown to influence biological processes. The virus-encoded G4s are affected by the mutational landscape leading to the formation/deletion of these G4s. Therefore, understanding and predicting these multivariate effects on traditional and non-traditional quadruplexes forms an important area of research, that is, yet to be investigated. We have designed a user-friendly webserver QUFIND (http://soodlab.com/qufinder/) that can predict traditional as well as non-traditional quadruplexes in a given sequence. QUFIND is connected with ENSEMBL and NCBI so that the sequences can be fetched in a real-time manner. The algorithm is designed in such a way that the user is provided with multiple options to customize the base (A, T, G, or C), size of the stem (2–5), loop length (1–30), number of bulges (1–5) as well as the number of mismatches (0–2) enabling the identification of any of the secondary structure as per their interest. QUFIND is designed to predict both CpG islands as well as G4s in a given sequence. Since G4s are very short as compared to the CpG islands, hence, QUFIND can also predict the overlapping G4s within CpG islands. Therefore, the user has the flexibility to identify either overlapping or non-overlapping G4s along with the CpG islands. Additionally, one section of QUFIND is dedicated to comparing the G4s in two viral sequences. The visualization is designed in such a manner that the user is able to see the unique quadruplexes in both the input sequences. The efficiency of QUFIND is calculated on G4s obtained from G4 high throughput sequencing data (n = 1000) or experimentally validated G4s (n = 329). Our results revealed that QUFIND is able to predict G4-quadruplexes obtained from G4-sequencing data with 90.06% prediction accuracy whereas experimentally validated quadruplexes were predicted with 97.26% prediction accuracy.
... Furthermore, their various conformations (parallel, antiparallel, hybrid-I and II) are not constant but could undergo conversion when the environmental conditions change [20]. With the development of experimental techniques like nuclear magnetic resonance (NMR), circular dichroism (CD), and gel electrophoresis, some interesting nontypical tetrads have been recently observed, namely A-/C-/U-and T-tetrads [21][22][23][24][25][26][27][28][29][30]. These are commonly stacked over the adjacent G-quartets and add significantly to the structural diversity and recognition especially in telomeres. ...
Quadruplexes (GQs), peculiar DNA/RNA motifs concentrated in specific genomic regions, play a vital role in biological processes including telomere stability and, hence, represent promising targets for anticancer therapy. GQs are formed by folding guanine-rich sequences into square planar G-tetrads which stack onto one another. Metal cations, most often potassium, further stabilize the architecture by coordinating the lone electron pairs of the O atoms. The presence of additional nucleic acid bases, however, has been recently observed experimentally and contributes substantially to the structural heterogeneity of quadruplexes. Therefore, it is of paramount significance to understand the factors governing the underlying complex processes in these structures. The current study employs DFT calculations to model the interactions between metal cations (K+, Na+, Sr2+) and diverse tetrads composed of a guanine layer in combination with a guanine (G)-, adenine (A)-, cytosine (C)-, thymine (T)-, or uracil (U)-based tetrad layer. Moreover, the addition of 4-(3,4-dihydroisoquinolin-2-yl)-2-(quinolin-2-yl)quinazoline to the modeled quadruplexes as a possible mechanism of its well-exerted antitumor effect is assessed. The calculations imply that the metal cation competition and ligand complexation are influenced by the balance between electronic and implicit/explicit solvation effects, the composition of the tetrad layers, as well as by the solvent exposure to the surrounding environment expressed in terms of different dielectric constant values. The provided results significantly enhance our understanding of quadruplex diversity, ligand recognition, and the underlying mechanisms of stabilization at an atomic level.
... In addition to Cd 2+ , DNA aptamers have also been widely used in the detection of other heavy metal ions, such as Hg 2+ , Pb 2+ and Ag + (41)(42)(43). The structures of many DNA aptamers complexed with metals such as Hg 2+ , Pb 2+ and Ag + have been reported (44)(45)(46)(47)(48)(49)(50), which reveal the detailed mechanistic explanation on the metalaptamer interactions. However, due to the lack of Cd 2+bound aptamer structure, how Cd 2+ is recognized by the aptamer remains elusive. ...
... Moreover, it also coordinates with two water molecules, which further stabilizes the conformation of the Cd 2+ ion ( Figure 2B). The coordinating mode of Cd 2+ is very different from that of Hg 2+ , Pb 2+ and Ag + observed in their aptamer structures (44)(45)(46)(47)(48)(49)(50). Compared to Hg 2+ and Ag + , the average coordinating distance (2.4Å) of Cd 2+ is slightly longer; however, it is ∼0.2Å shorter than the Pd 2+ -coordinating distance. ...
... However, the DNA1-Cd 2+ coordinating mode is very different from those between aptamers and other heavy metal ions. As observed in their complex structures, Hg 2+ and Ag + mainly form metallo-base pairs with pyrimidinepyrimidine (T-T, C-T and C-C) or purine-purine (G-G) mispairs (46)(47)(48)(49)(50), whereas Pb 2+ is recognized by Gquadruplexes (44,59) or DNAzymes (45). In addition to the DNA strand, recognition of Pd 2+ by DNAzyme also requires one substrate RNA strand. ...
Cadmium (Cd) is one of the most toxic heavy metals. Exposure to Cd can impair the functions of the kidney, respiratory system, reproductive system and skeletal system. Cd2+-binding aptamers have been extensively utilized in the development of Cd2+-detecting devices; however, the underlying mechanisms remain elusive. This study reports four Cd2+-bound DNA aptamer structures, representing the only Cd2+-specific aptamer structures available to date. In all the structures, the Cd2+-binding loop (CBL-loop) adopts a compact, double-twisted conformation and the Cd2+ ion is mainly coordinated with the G9, C12 and G16 nucleotides. Moreover, T11 and A15 within the CBL-loop form one regular Watson-Crick pair and stabilize the conformation of G9. The conformation of G16 is stabilized by the G8-C18 pair of the stem. By folding and/or stabilizing the CBL-loop, the other four nucleotides of the CBL-loop also play important roles in Cd2+ binding. Similarly to the native sequence, crystal structures, circular dichroism spectrum and isothermal titration calorimetry analysis confirm that several variants of the aptamer can recognize Cd2+. This study not only reveals the underlying basis for the binding of Cd2+ ions with the aptamer, but also extends the sequence for the construction of novel metal-DNA complex.
... Intriguingly, there is an unexplained bias for G/C-rich open chromatin and nucleosome depleted regions in G4s landscape datasets and the same G/C-rich regions are predominantly the binding sites for the G4s-binding proteins (unpublished observations derived from data published vide 33 ). In addition, tetrads formed by non-G nucleotides also exist interspersed between G tetrads with some even stabilizing the G4s to varying degrees [34][35][36][37] . It remains unknown if the G/C-rich and non-G/C-rich G4s are regulated by same or distinct mechanisms. ...
Our understanding of DNA G-quadruplexes (G4s) from in vitro studies has been complemented by genome-wide G4 landscapes from cultured cells. Conventionally, formation of G4s is accepted to depend on G-repeats such that they form tetrads. However, genome-wide G4s characterized through high-throughput sequencing suggests that these structures form at a large number of regions with no such canonical G4-forming signatures. New functions, such as regulation of gene expression regulation and replication have been attributed to the genomic G4s. Many G4-binding proteins have been described, but their roles in formation and maintenance of G4s remain unknown. The representation of G4s not bound to proteins in these genomic landscapes remains unaddressed. We have developed a simple variation of the conventional G4-chromatin immunoprecipitation (G4-ChIP) assay to capture G4s in the cells using the 1H6 antibody. A comparison with the conventional G4-ChIP and in vitro DNA pull-down assays shows that our method minimizes false G4 detection. We use this method along with a transfected or in vitro-added control DNA (containing canonical G4-forming sequences) to study the G4 regulatory effects of the CGG repeat-binding protein CGGBP1. We present a reliable G4 landscape and apply the new protocol to discover a functionally relevant regulation of G4s by CGGBP1. Our results show that sharp interstrand transitions of G/C-skew, rich in binding sites for CTCF and CGGBP1, form G4s. Thus, our method demonstrates a sequence property-specific constraints of the nuclear environment that mitigates G4 formation.
... The latter can involve canonical G:C or A:T Watson-Crick base pairs, or a variety of mismatches. The overall size of T-, C-and A-tetrads, as estimated from diagonal C1'-C1' distance, is slightly smaller than in the case of the G-tetrad, being this distance around 1-2 Å shorter in T-and A-tetrads, and ~3 Å shorter in the case of the C-tetrad [14]. Due to their similar size, homotetrads provoke only minor distortions in the structure of parallel G-quadruplexes. ...
... Of particular interest is the case of the oligonucleotide of sequence d (AGAGA-GATGGGTGCGTT), which folds as a tetrameric parallel quadruplex. In this case, the four possible DNA homotetrads coexist in the same crystal structure [14]. Homotetrads have also been found in RNA G-quadruplex scaffolds. ...
... This tetrad is mainly stabilized by hydrogen bonds between imino protons H(N3) and O4 atoms of adjacent thymines. However, Liu et al. [14] suggested that weak hydrogen bond interactions between H(C5) and O2 atoms may also contribute to the stability. Similar T-tetrads have been observed in the crystal structure of d(TGGGGT) 4 [22] and in an all-LNA G-quadruplex from 5 -TGGGT-3 . ...
Tetrads (or quartets) are arrangements of four nucleobases commonly involved in the stability of four-stranded nucleic acids structures. Four-stranded or quadruplex structures have attracted enormous attention in the last few years, being the most extensively studied guanine quadruplex (G-quadruplex). Consequently, the G-tetrad is the most common and well-known tetrad. However, this is not the only possible arrangement of four nucleobases. A number of tetrads formed by the different nucleobases have been observed in experimental structures. In most cases, these tetrads occur in the context of G-quadruplex structures, either inserted between G-quartets, or as capping elements at the sides of the G-quadruplex core. In other cases, however, non-G tetrads are found in more unusual four stranded structures, such as i-motifs, or different types of peculiar fold-back structures. In this report, we review the diversity of these non-canonical tetrads, and the structural context in which they have been found.
... Structural work demonstrates great versatility of adenines. Their availability may lead to formation of A-only tetrads, [13][14][15] GAGA tetrads, 16 or unique pentads, [17][18] hexads, 19 and heptads, [20][21] where the traditional G-tetrad is coordinated in plane by 1-3 adenines at the groove positions. Biological evidence suggests that purine-only sequences are widely distributed throughout the human genome and are located near gene promoters, in telomeres, centromeres, triplet repeat disease sequences, or recombination hotspot sites. ...
... The traditional G-tetrad is a robust building block because its bases are engaged in four hydrogen bonds, two on their Watson-Crick side and two on their Hoogsteen side, leading to eight hydrogen bonds in total, Fig. 7C. Bases in non-guanine tetrads, such as cytosine, 14 adenine, [13][14][15] and uracil tetrads 13 (non-G tetrads were recently reviewed 54 ) are connected by a single hydrogen bond, leading to four hydrogen bonds in total and lower stability of the arrangements. The lack of hydrogen bonding in our symmetry tetrad questions its validity, but its existence in two different structures supports its credibility. ...
... The traditional G-tetrad is a robust building block because its bases are engaged in four hydrogen bonds, two on their Watson-Crick side and two on their Hoogsteen side, leading to eight hydrogen bonds in total, Fig. 7C. Bases in non-guanine tetrads, such as cytosine, 14 adenine, [13][14][15] and uracil tetrads 13 (non-G tetrads were recently reviewed 54 ) are connected by a single hydrogen bond, leading to four hydrogen bonds in total and lower stability of the arrangements. The lack of hydrogen bonding in our symmetry tetrad questions its validity, but its existence in two different structures supports its credibility. ...
The Ras‐Raf‐MEK‐ERK (MAPK) pathway is a signal transduction cascade used to regulate cellular processes including cell cycle progression and proliferation. Aberrant activation of this pathway is implicated in cancer development, and treatment with Raf, MEK and ERK inhibitors often leads to adaptive resistance. Combination therapies have been shown to offer benefits; however, the MEK‐ERK interface remains poorly understood, hindering structure‐guided approaches to the design of potent MAPK pathway inhibitors targeting this complex.
To identify important residues for the MEK1‐ERK2 interaction, we performed site‐directed mutagenesis on ERK2. We used circular dichroism to assess the secondary structure of the ERK2 mutants. We also used biolayer interferometry binding experiments coupled with phosphorylation assays to evaluate the impact of the mutated residues on the formation of the MEK1‐ERK2 complex and activity.
Circular dichroism showed no differences in secondary structure for any of our ERK2 mutants. Of all the mutations generated, the L234D mutation in ERK abrogated binding and phosphorylation by MEK1 the most. Other mutants showed some reductions in binding or activity but require further analysis. Of note, L234 is located on an ERK2 α‐helix adjacent to the phosphorylation lip, consistent with MEK1 binding this face during phosphorylation. Our results suggest that this α‐helix may play critical roles in the MEK1‐ERK2 complex. Studying the impact of additional mutations in this and additional regions will develop our understanding of the MEK‐ERK interface and inform the design of allosteric inhibitors that can modulate MEK‐ERK complex formation.
... That formaldehyde is a passive DNA denaturing agent [34,35] entails that protein unbound G4s would be underrepresented in the G4-ChIP. In addition, tetrads formed by non-G nucleotides also exist interspersed between G tetrads, with some even stabilizing the G4s to varying degrees [36][37][38][39]. Currently, we do not know if the large fraction of DNA pulled down by antibodies specific for G4s that does not show any (G 3 -N (1)(2)(3)(4)(5)(6)(7) )xn signature is an artifact or not. ...
... Yet, Liu et al. showed that this motif in a solution of Pb 2+ and several monovalent cations bound only one Pb 2+ cationthe cation in the adjacent vacancy was found to be Na + . 42 Since two chelation sites of the (GCG) 4 quadruplex have distinct coordination geometries (bipyramidal antiprismatic and nearly square prismatic), Liu et al. argued that Pb 2+ coordination might depend on the quartet orientation. 42 This observation motivated us to examine bond energies of Na + and Ca 2+ cations in the (GCG) 4 quadruplex. ...
... 42 Since two chelation sites of the (GCG) 4 quadruplex have distinct coordination geometries (bipyramidal antiprismatic and nearly square prismatic), Liu et al. argued that Pb 2+ coordination might depend on the quartet orientation. 42 This observation motivated us to examine bond energies of Na + and Ca 2+ cations in the (GCG) 4 quadruplex. We computed these energies at the geometries of Ba 2+ cations in quadruplex 6. ...
