Bulges in left-handed G-quadruplexes

Das, Poulomi; Ngo, Khac Huy; Winnerdy, Fernaldo Richtia; Maity, Arijit; Bakalar, Blaž; Mechulam, Yves; Schmitt, Emmanuelle; Phan, Anh Tuân

doi:10.1093/nar/gkaa1259

Cited by 15 publications

(11 citation statements)

References 70 publications

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“…S7, ESI †). 50 Due to its linear nature, with diameter smaller than the distance between adjacent capping thymines, spermine is able to reside in the cavity between the capping thymines (Fig. S7, ESI †).…”

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confidence: 99%

Tetrad-binding ligands do not bind specifically to left-handed G-quadruplexes

Das

Phan

2022

Chem. Commun.

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confidence: 99%

Tetrad-binding ligands do not bind specifically to left-handed G-quadruplexes

Das

Phan

2022

Chem. Commun.

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“…[10] In addition to this canonical G4 structural polymorphism, new aspects of structural complexity have been described recently, which are referred to as non-canonical polymorphism. [2,[11][12][13] Aspects including bulges, [14][15][16] exceptional loop arrangements [17,18] and snap-back motifs [19][20][21][22][23] can be observed in G4s from sequences that do not comply with the narrow definition given above (Figure 1, III).…”

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confidence: 99%

Folding dynamics of polymorphic G‐quadruplex structures

Grün

Schwalbe

2021

Biopolymers

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G-quadruplexes (G4), found in numerous places within the human genome, are involved in essential processes of cell regulation. Chromosomal DNA G4s are involved for example, in replication and transcription as first steps of gene expression. Hence, they influence a plethora of downstream processes. G4s possess an intricate structure that differs from canonical B-form DNA. Identical DNA G4 sequences can adopt multiple long-lived conformations, a phenomenon known as G4 polymorphism. A detailed understanding of the molecular mechanisms that drive G4 folding is essential to understand their ambivalent regulatory roles.Disentangling the inherent dynamic and polymorphic nature of G4 structures thus is key to unravel their biological functions and make them amenable as molecular targets in novel therapeutic approaches. We here review recent experimental approaches to monitor G4 folding and discuss structural aspects for possible folding pathways. Substantial progress in the understanding of G4 folding within the recent years now allows drawing comprehensive models of the complex folding energy landscape of G4s that we herein evaluate based on computational and experimental evidence.

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“…We have reported on the first solution structure of intramolecular G4s formed by G4-S containing a single (or more) non-G nucleotide insertion(s) in G-stems, and we also have presented evidence that such non-guanine base ‘bulge’ containing sequences can fold into thermodynamically stable G4s with one or more bulges (G4-B) of diverse spatial variations. Recent works by our team members have further broadened the definition of potential G4-B forming sequences (pG4-BS) ( 48 , 49 ). Overall, these results provide in vitro experimental evidence that G4-S with a varying number, size, and type of bulges could exist and be capable of forming stable G4-B.…”

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confidence: 99%

Stable bulged G-quadruplexes in the human genome: identification, experimental validation and functionalization

Papp

Mukundan

Jenjaroenpun

et al. 2023

Nucleic Acids Research

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DNA sequence composition determines the topology and stability of G-quadruplexes (G4s). Bulged G-quadruplex structures (G4-Bs) are a subset of G4s characterized by 3D conformations with bulges. Current search algorithms fail to capture stable G4-B, making their genome-wide study infeasible. Here, we introduced a large family of computationally defined and experimentally verified potential G4-B forming sequences (pG4-BS). We found 478 263 pG4-BS regions that do not overlap ‘canonical’ G4-forming sequences in the human genome and are preferentially localized in transcription regulatory regions including R-loops and open chromatin. Over 90% of protein-coding genes contain pG4-BS in their promoter or gene body. We observed generally higher pG4-BS content in R-loops and their flanks, longer genes that are associated with brain tissue, immune and developmental processes. Also, the presence of pG4-BS on both template and non-template strands in promoters is associated with oncogenesis, cardiovascular disease and stemness. Our G4-BS models predicted G4-forming ability in vitro with 91.5% accuracy. Analysis of G4-seq and CUT&Tag data strongly supports the existence of G4-BS conformations genome-wide. We reconstructed a novel G4-B 3D structure located in the E2F8 promoter. This study defines a large family of G4-like sequences, offering new insights into the essential biological functions and potential future therapeutic uses of G4-B.

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Bulges in left-handed G-quadruplexes

Cited by 15 publications

References 70 publications

Tetrad-binding ligands do not bind specifically to left-handed G-quadruplexes

Tetrad-binding ligands do not bind specifically to left-handed G-quadruplexes

Folding dynamics of polymorphic G‐quadruplex structures

Stable bulged G-quadruplexes in the human genome: identification, experimental validation and functionalization

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