Fundamental aspects of the nucleic acid i-motif structures

Benabou, Sanae; Aviñó, Anna; Eritja, Ramón; González, Carlos; Gargallo, Raimundo

doi:10.1039/c4ra02129k

Cited by 161 publications

(179 citation statements)

References 198 publications

(470 reference statements)

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“…Other contexts of the i-motif core such as d(ACCCT) [28] and d(TAACCC) [29] provide additional structural evidence that non-C•C + bases at either end of the motif play an important role in stabilizing these novel DNA secondary structures. Most studies on i-motifs show that temperature, pH, and the length of C-tracts affected the lifetime and stability of the tetrameric i-motif [8,11]. This is consistent with our previous observations [30,31].…”

Section: Introductionsupporting

confidence: 82%

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Formation and Dissociation of the Interstrand i-Motif by the Sequences d(X_nC₄Y_m) Monitored with Electrospray Ionization Mass Spectrometry

Cao

Qin

Bruist

et al. 2015

J. Am. Soc. Mass Spectrom.

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Abstract. Formation and dissociation of the interstrand i-motifs by DNA with the sequence d(X n C 4 Y m ) (X and Y represent thymine, adenine, or guanine, and n, m range from 0 to 2) are studied with electrospray ionization mass spectrometry (ESI-MS), circular dichroism (CD), and UV spectrophotometry. The ion complexes detected in the gas phase and the melting temperatures (T m ) obtained in solution show that a non-C base residue located at 5′ end favors formation of the four-stranded structures, with T > A > G for imparting stability. Comparatively, no rule is found when a non-C base is located at the 3′ end. Detection of penta-and hexa-stranded ions indicates the formation of i-motifs with more than four strands. In addition, the i-motifs seen in our mass spectra are accompanied by single-, double-, and triple-stranded ions, and the trimeric ions were always less abundant during annealing and heat-induced dissociation process of the DNA strands in solution (pH=4.5). This provides a direct evidence of a strand-by-strand formation and dissociation pathway of the interstrand i-motif and formation of the triple strands is the rate-limiting step. In contrast, the trimeric ions are abundant when the tetramolecular ions are subjected to collision-induced dissociation (CID) in the gas phase, suggesting different dissociation behaviors of the interstrand i-motif in the gas phase and in solution. Furthermore, hysteretic UV absorption melting and cooling curves reveal an irreversible dissociation and association kinetic process of the interstrand i-motif in solution.

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Section: Introductionsupporting

confidence: 82%

“…These sequences may form four-stranded DNA structures featuring G-quadruplexes [2][3][4][5][6] and i-motifs [7][8][9]. When predicting the likelihood of a duplex DNA with runs of Gs and Cs forming an alternative structure in vivo, the energetics and kinetics of the folding of both the Grich and the C-rich strand must be understood.…”

Section: Introductionmentioning

confidence: 99%

Formation and Dissociation of the Interstrand i-Motif by the Sequences d(X_nC₄Y_m) Monitored with Electrospray Ionization Mass Spectrometry

Cao

Qin

Bruist

et al. 2015

J. Am. Soc. Mass Spectrom.

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“…1 A-C). The sequences complementary to regions capable of G4 formation are composed of tandem repeats of cytosine, and these C-rich regions can form a different type of tetraplex topology, which is the i-motif (10,11). An intramolecular i-motif is formed upon the interaction of four C-rich regions.…”

mentioning

confidence: 99%

Topological impact of noncanonical DNA structures on Klenow fragment of DNA polymerase

Takahashi

Brazier

Sugimoto

2017

Proc. Natl. Acad. Sci. U.S.A.

108

113

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Noncanonical DNA structures that stall DNA replication can cause errors in genomic DNA. Here, we investigated how the noncanonical structures formed by sequences in genes associated with a number of diseases impacted DNA polymerization by the Klenow fragment of DNA polymerase. Replication of a DNA sequence forming an i-motif from a telomere, hypoxia-induced transcription factor, and an insulin-linked polymorphic region was effectively inhibited. On the other hand, replication of a mixed-type G-quadruplex (G4) from a telomere was less inhibited than that of the antiparallel type or parallel type. Interestingly, the i-motif was a better inhibitor of replication than were mixed-type G4s or hairpin structures, even though all had similar thermodynamic stabilities. These results indicate that both the stability and topology of structures formed in DNA templates impact the processivity of a DNA polymerase. This suggests that i-motif formation may trigger genomic instability by stalling the replication of DNA, causing intractable diseases.oncanonical intramolecular structures of nucleic acids, such as a triplex and a quadruplex, are stabilized under conditions that mimic the crowded cellular conditions (1), and have been detected in cells (2, 3). In vitro and in vivo, guaninequadruplex (G-quadruplex or G4) formation inhibits transcription and translation of template nucleic acids (4-8). It is possible that the noncanonical structures act as "functional codes" triggered by different molecular environments, which regulate gene expression epigenetically (6, 7). As sequences capable of forming the noncanonical structures are found in telomeres and promoter regions of known oncogenes, alterations of the noncanonical structures could play important roles in the progression of cancer and in other diseases (9).One of the remarkable features of noncanonical structures of nucleic acids is the diversity of topologies. In the case of G4s, antiparallel, mixed, and parallel type structures have been characterized ( Fig. 1 A-C). The sequences complementary to regions capable of G4 formation are composed of tandem repeats of cytosine, and these C-rich regions can form a different type of tetraplex topology, which is the i-motif (10, 11). An intramolecular i-motif is formed upon the interaction of four C-rich regions. The structure has three loops and two parallel-stranded hairpin-like units stabilized by cytosine and protonated cytosine (C:C + ) base pairs that are vertically intercalated antiparallel to one another ( Fig. 1 D and E). The i-motif structures are categorized into class I and class II based on the lengths of the loops. C-rich sequences are found in telomeres and in the promoter regions of about 40% of human genes (12, 13). As the i-motif is stabilized by hydrogen bonding in C:C + base pairs (14, 15), acidic conditions stabilize the structure. As the i-motif can mediate transcriptional regulation of B-cell lymphoma 2 (Bcl2) oncogene in cells (16), the environment inside these cells might be favorable to i-motif formation....

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“…In acidic pH, all the spectra exhibited positive Cotton effect with peak at 288 and negative Cotton effect with weak peak at 262 nm. These two bands are characteristic for an i-motif secondary structure, however the exact position of these bands is dependent on the nature of bases located at the loops [12]. Furthermore, we could not detect an induced CD signal at 340 nm in any case.…”

Section: Formation Of I-motifs By Pyrene-modified Ret Sequencesmentioning

confidence: 61%

“…The i-motif structure is constructed as a consequence of the intercalation of two hemiprotonated C-C+ base-paired duplexes. Both intra-and intermolecular i-motifs can be created by C-rich oligonucleotides depending mainly on the amount of cytosine tracks and surrounding conditions [6,11,12].…”

Section: Open Accessmentioning

confidence: 99%

Steady-State Fluorescence and Lifetime Emission Study of pH-Sensitive Probes Based on i-motif Forming Oligonucleotides Single and Double Labeled with Pyrene

2015

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Cytosine-rich nucleic acids undergo pH-stimulated structural transitions leading to formation of an i-motif architecture at an acidic pH. Thus, i-motifs are good foundation for designing simple pH-sensitive fluorescent probes. We report here steady-state and time-resolved fluorescence studies of pyrene-labeled probes based on RET sequence: C4GC4GC4GC4TA (RET21), AC4GC4GC4GC4TA (RET21A) and C4GC4GC4GC4T (RET20). Comparative studies with single-and double-labeled i-motif probes were carried out. For each probe, we have measured fluorescence spectra and decays for emission wavelength of 390 nm over a wide range of pH (from 4.0 to 8.0). Effect of the oligonucleotide sequence and the number of pyrene labels on the spectral characteristics of probes were discussed.

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Fundamental aspects of the nucleic acid i-motif structures

Abstract: The latest research on fundamental aspects of i-motif structures is reviewed with special attention to their hypothetical rolein vivo.

Cited by 161 publications

References 198 publications

Formation and Dissociation of the Interstrand i-Motif by the Sequences d(X_nC₄Y_m) Monitored with Electrospray Ionization Mass Spectrometry

Formation and Dissociation of the Interstrand i-Motif by the Sequences d(X_nC₄Y_m) Monitored with Electrospray Ionization Mass Spectrometry

Topological impact of noncanonical DNA structures on Klenow fragment of DNA polymerase

Steady-State Fluorescence and Lifetime Emission Study of pH-Sensitive Probes Based on i-motif Forming Oligonucleotides Single and Double Labeled with Pyrene

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Fundamental aspects of the nucleic acid i-motif structures

Abstract: The latest research on fundamental aspects of i-motif structures is reviewed with special attention to their hypothetical rolein vivo.

Cited by 161 publications

References 198 publications

Formation and Dissociation of the Interstrand i-Motif by the Sequences d(XnC4Ym) Monitored with Electrospray Ionization Mass Spectrometry

Formation and Dissociation of the Interstrand i-Motif by the Sequences d(XnC4Ym) Monitored with Electrospray Ionization Mass Spectrometry

Topological impact of noncanonical DNA structures on Klenow fragment of DNA polymerase

Steady-State Fluorescence and Lifetime Emission Study of pH-Sensitive Probes Based on i-motif Forming Oligonucleotides Single and Double Labeled with Pyrene

Contact Info

Product

Resources

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Formation and Dissociation of the Interstrand i-Motif by the Sequences d(X_nC₄Y_m) Monitored with Electrospray Ionization Mass Spectrometry

Formation and Dissociation of the Interstrand i-Motif by the Sequences d(X_nC₄Y_m) Monitored with Electrospray Ionization Mass Spectrometry