A thermodynamic overview of naturally occurring intramolecular DNA quadruplexes

Kumar, Niti; Maiti, Souvik

doi:10.1093/nar/gkn543

Cited by 76 publications

(82 citation statements)

References 63 publications

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“…We did not observe a plateau around a total loop length of ≈7 nt as found by Bugaut and Balasubramanian (17): T m tends to reach a plateau but only for much longer loops (Figures 6 and 7A). The correlation found in Figure 7A is strikingly better than the one observed for naturally occurring sequences (24). In the later case, loop composition plays a predominant role and masks the length effects.…”

Section: Discussioncontrasting

confidence: 52%

How long is too long? Effects of loop size on G-quadruplex stability

Guédin

Gros

Alberti

et al. 2010

Nucleic Acids Research

385

350

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We compared here 80 different sequences containing four tracts of three guanines with loops of variable length (between 1 and 15 bases for unmodified sequences, up to 30 for fluorescently labeled oligonucleotides). All sequences were capable of forming stable quadruplexes, with Tm above physiological temperature in most cases. Unsurprisingly, the melting temperature was systematically lower in sodium than in potassium but the difference between both ionic conditions varied between 1 and >39°C (average difference: 18.3°C). Depending on the sequence context, and especially for G4 sequences involving two very short loops, the third one may be very long without compromising the stability of the quadruplex. A strong inverse correlation between total loop length and Tm was found in K+: each added base leads to a 2°C drop in Tm or ∼0.3 kcal/mol loss in ΔG°. The trend was less clear in Na+, with a longer than expected optimal loop length (up to 5 nt). This study will therefore extend the sequence repertoire of quadruplex-prone sequences, arguing for a modification of the widely used consensus (maximal loop size of 7 bases).

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Section: Discussioncontrasting

confidence: 52%

How long is too long? Effects of loop size on G-quadruplex stability

Guédin

Gros

Alberti

et al. 2010

Nucleic Acids Research

385

350

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“…As compared to duplex DNA, G4s are normally less stable (reviewed in [4], [62], [63]). Thus, high G4 content (abundance) in a particular TRR can enhance the competition of G4 DNA with adjacent duplex DNA, resulting in the increased probability of the involvement of G4s in regulating downstream gene expression.…”

Section: Resultsmentioning

confidence: 99%

“…Both have similar thermal stability (Table 6) as compared to the human telomeric G4 [77], [78], and other G4s with similar loop length, such as MYC, KIT, WNT1 and VEGF G4s [4]. Kinetic stability studies (Table S3) revealed that the unfolding of MNSG4 is entropically driven and that it can unfold relatively easily [79], [80].…”

Section: Discussionmentioning

confidence: 99%

“…As compared to other non-B-form DNA, G4s are relatively stable in solution under near-physiological conditions (thermodynamic and kinetic stability of G4s are reviewed in [4] and [5], respectively), which enables them to compete with adjacent duplex DNA and therefore participate in certain biological processes. The accumulated distribution of G4s in gene promoter regions throughout the human genome also makes them particularly important as compared to other non-B-form DNA structures [6].…”

Section: Introductionmentioning

confidence: 99%

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Possible Regulatory Roles of Promoter G-Quadruplexes in Cardiac Function-Related Genes – Human TnIc as a Model

et al. 2013

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G-quadruplexes (G4s) are four-stranded DNA secondary structures, which are involved in a diverse range of biological processes. Although the anti-cancer potential of G4s in oncogene promoters has been thoroughly investigated, the functions of promoter G4s in non-cancer-related genes are not well understood. We have explored the possible regulatory roles of promoter G4s in cardiac function-related genes using both computational and a wide range of experimental approaches. According to our bioinformatics results, it was found that potential G4-forming sequences are particularly enriched in the transcription regulatory regions (TRRs) of cardiac function-related genes. Subsequently, the promoter of human cardiac troponin I (TnIc) was chosen as a model, and G4s found in this region were subjected to biophysical characterisations. The chromosome 19 specific minisatellite G4 sequence (MNSG4) and near transcription start site (TSS) G4 sequence (−80 G4) adopt anti-parallel and parallel structures respectively in 100 mM KCl, with stabilities comparable to those of oncogene G4s. It was also found that TnIc G4s act cooperatively as enhancers in gene expression regulation in HEK293 cells, when stabilised by a synthetic G4-binding ligand. This study provides the first evidence of the biological significance of promoter G4s in cardiac function-related genes. The feasibility of using a single ligand to target multiple G4s in a particular gene has also been discussed.

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“…Previous works support the important role played by the nature and length of the loops in quadruplex stability (12–22) and reports suggest a strong influence of loop length on quadruplex stability. However, the stability cannot simply be deduced from total loop length, as elegantly demonstrated by Kumar and Maiti (21). …”

Section: Introductionmentioning

confidence: 99%

Stability of intramolecular quadruplexes: sequence effects in the central loop

Guédin¹,

Alberti²,

Mergny³

2009

Nucleic Acids Research

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Hundreds of thousands of putative quadruplex sequences have been found in the human genome. It is important to understand the rules that govern the stability of these intramolecular structures. In this report, we analysed sequence effects in a 3-base-long central loop, keeping the rest of the quadruplex unchanged. A first series of 36 different sequences were compared; they correspond to the general formula GGGTTTGGGHNHGGGTTTGGG. One clear rule emerged from the comparison of all sequence motifs: the presence of an adenine at the first position of the loop was significantly detrimental to stability. In contrast, adenines have no detrimental effect when present at the second or third position of the loop. Cytosines may either have a stabilizing or destabilizing effect depending on their position. In general, the correlation between the Tm or ΔG° in sodium and potassium was weak. To determine if these sequence effects could be generalized to different quadruplexes, specific loops were tested in different sequence contexts. Analysis of 26 extra sequences confirmed the general destabilizing effect of adenine as the first base of the loop(s). Finally, analysis of some of the sequences by microcalorimetry (DSC) confirmed the differences found between the sequence motifs.

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A thermodynamic overview of naturally occurring intramolecular DNA quadruplexes

Cited by 76 publications

References 63 publications

How long is too long? Effects of loop size on G-quadruplex stability

How long is too long? Effects of loop size on G-quadruplex stability

Possible Regulatory Roles of Promoter G-Quadruplexes in Cardiac Function-Related Genes – Human TnIc as a Model

Stability of intramolecular quadruplexes: sequence effects in the central loop

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