G-quadruplex structure of an anti-proliferative DNA sequence

Quang, Ngoc; Chung, Wan Jun; Truong, Thi Hong Anh; Heddi, Brahim; Phan, Anh Tuân

doi:10.1093/nar/gkx274

Cited by 87 publications

(85 citation statements)

References 41 publications

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“…Such stems can be stably formed only with the help of additional stabilizing interactions, such as dimerization and linked two-quartet parallel-stranded DNA GQs. 43 Nevertheless, it does not preclude occurrence of parallel-stranded two-quartet stems in transitory ensembles during folding processes. Antiparallel DNA two-quartet stems as well as RNA two-quartet stems are structurally considerably more stable than the parallel DNA two-quartet stems, although even these species likely require additional stabilizing elements to achieve a detectable thermodynamic stability.…”

Section: Resultsmentioning

confidence: 99%

Stability of Two-quartet G-quadruplexes and Their Dimers in Atomistic Simulations

Islam

Stadlbauer

Vorlı́čková

et al. 2019

Preprint

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G-quadruplexes (GQ) are four-stranded non-canonical DNA and RNA architectures that can be formed by guanine-rich sequences. The stability of GQs increases with the number of G-quartets and three G-quartets generally form stable GQs. However, stability of two-quartet GQs is an open issue. To understand the intrinsic stability of two-quartet GQ stems, we have carried out a expression. 5 Therefore, there is considerable interest in studying and modulating the formation of GQs as a means for controlling gene expression and other cellular processes. 6 GQs are formed by stacking of planar guanine quartets, creating the G-stem. The O6 atoms of all the guanines face to form a central electron-rich channel within the GQ where cations bind and coordinate with the O6 atoms. This coordination is essential for GQ stability. 7 Bases not involved in G-stem belong to bulges, flanking nucleotides or participate in the loops linking the G-strands of the GQs. 3The GQs can be monomolecular, bimolecular or tetramolecular depending on the number of DNA or RNA molecules that form the GQ. 8,9 The topologies of GQs are highly variable as the G-strand orientation can be parallel or antiparallel and based on that GQs can fold into parallel, antiparallel or hybrid topology. 10,11 The guanines in the DNA GQs can adopt syn or anti orientation. 10,12,13 In the RNA GQs, the 2 -hydroxyl group in ribose allows for more interactions with the bases, cations and water molecules thereby increasing their stability, as common in RNA molecules. [14][15][16][17][18][19] It also restricts the orientation of the guanine bases favouring the anti-orientation. 14 Therefore, the majority of the RNA GQs have been observed in the parallel-stranded topology with all bases in the anti-orientation. [15][16][17][18] The loops further add to the diversity as the GQs can have propeller, lateral or diagonal loops. 8,[20][21][22][23][24][25][26][27] The parallel-stranded GQ have propeller (double-chain reversal) loops as they are necessary to orient the following and preceding G-strands in a parallel arrangement. 8 The antiparallel and hybrid GQs can have various combinations of the three loop types. [20][21][22][23][24][25][26][27] The overall GQ topology dictates the loop combination as well as the allowable syn-anti patterns of the guanines. Na + ions tend to coordinate within the plane while K + ions coordinate between the planes of the G-quartets. 28,29 The cation-quadruplex interactions can induce kinetic and equilibrium differences between the different topologies. 28,30,31 Stability of GQs is affected by the number of G-quartets in the stem. 14,[32][33][34] It is commonly accepted that increasing the number of G-quartets usually stabilizes the GQ structure. 12,14,34,35 In DNA, stable GQ structures generally involve three quartets or more, although stable antiparallel two-quartet GQs with loop alignments or stacked triads have also been observed. 21, 36 27 In such GQs, additional interactions formed by the loops or triads above and/or below the G-stems contribut...

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Section: Resultsmentioning

confidence: 99%

Stability of Two-quartet G-quadruplexes and Their Dimers in Atomistic Simulations

Islam

Stadlbauer

Vorlı́čková

et al. 2019

Preprint

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“…Other cases of multiple loop substitutions in both blocks (Table 3) abolished the left-handed G-quadruplex formation ( Figure S15). Thes equence analysis of Z-G4 together with new experimental evidence shows that as horter motif of 12-nt GT(GGT) 3 Gissufficient for the formation of aG-quadruplex with left-handed helicity.Itisalso this short motif that is able to change the helicity of the otherwise right-handed Gquadruplex forming Block1 within the structure of Z-G4.…”

Section: Angewandte Chemiementioning

confidence: 98%

“…[1] G-quadruplexes are involved in essential cellular processes. [2] Studies have shown that G-quadruplex-forming sequences possess anti-cancer [3] and anti-HIV [4] activities.Such peculiar structures have also been used in nanotechnology. [5] Several G-quadruplex folding topologies have been reported that differ according to their relative strand orientations and loop types.…”

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confidence: 99%

A Minimal Sequence for Left‐Handed G‐Quadruplex Formation

et al. 2019

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Recently,w eo bserved the first example of al efthanded G-quadruplex structure formed by natural DNA, named Z-G4. We analysed the Z-G4 structure and inspected its primary 28-nt sequence in order to identify motifs that convey the unique left-handed twist. Using circular dichroism spectroscopy, NMR spectroscopy, and X-rayc rystallography,w e revealed am inimal sequence motif of 12 nt (GTGGTGGTGGTG) for formation of the left-handed DNAG-quadruplex, which is found to be highly abundant in the human genome.Asystematic analysis of thymine loop mutations revealed am oderate sequence tolerance,w hich would further broaden the space of sequences prone to lefthanded G-quadruplex formation.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

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“…An anti‐cancer DNA aptamer containing 17 guanines AGRO100 (also known as AS1411 ) has been shown to adopt multiple G4 conformations . Single G‐to‐T substitutions at various positions of AGRO100 have resulted in the formation of distinct G4 structures . The substitution at position 11 ( AT11 ) generated a four‐layer parallel G4, while another substitution at position 27 ( AT27 ) resulted in a four‐layer parallel left‐handed G4.…”

Section: Figurementioning

confidence: 99%

An Unprecedented Knot‐like G‐Quadruplex Peripheral Motif

2019

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A knot‐like G‐quadruplex peripheral structure is formed by a 7‐nt DNA sequence DL7 (TGTTGGT), in which six out of its seven nucleobases participate in compact base‐pairing interactions. Here, the solution NMR structure of a 24‐nt DNA oligonucleotide containing the DL7 sequence shows the interaction between a two‐layer anti‐parallel G‐quadruplex core and the peripheral knot‐like structure, including the construction of two sharp turns in the DNA backbone. The formation of this novel structural element highlights the intricate properties of single‐stranded DNA folding in presence of G‐quadruplex‐forming motifs. We demonstrated the compatibility of the DL7 knot‐like structure with various G‐quadruplexes, which could have implications in drug design and DNA engineering.

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G-quadruplex structure of an anti-proliferative DNA sequence

Cited by 87 publications

References 41 publications

Stability of Two-quartet G-quadruplexes and Their Dimers in Atomistic Simulations

Stability of Two-quartet G-quadruplexes and Their Dimers in Atomistic Simulations

A Minimal Sequence for Left‐Handed G‐Quadruplex Formation

An Unprecedented Knot‐like G‐Quadruplex Peripheral Motif

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