Concentration-dependent conformational changes in GQ-forming ODNs

Li, Yang Yun; Abu-Ghazalah, Rashid M.; Zamiri, Bita; Macgregor, Robert B.

doi:10.1016/j.bpc.2016.02.002

Cited by 10 publications

(9 citation statements)

References 21 publications

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“…Indeed, it has been demonstrated using FRET that G-quadruplex-forming oligonucleotides introduced into human cells have different conformations in the nucleus, cytoplasm and nucleolus [ 119 ]. Also, even in the absence of crowding or dehydrating agents, very high concentrations of DNA induce a conversion of hybrid telomeric G-quadruplexes to a parallel form that is likely intermolecular [ 97 , 120 , 121 ], and divalent cations such as Ca 2+ and Sr 2+ can also promote formation of parallel G-quadruplexes [ 39 , 122 , 123 ]. An antibody that specifically recognizes parallel G-quadruplexes detected human telomeres both by immunofluorescence and chromatin immunoprecipitation, supporting the existence of parallel G-quadruplexes at human telomeres [ 124 , 125 ], although it should be remembered that these techniques do not distinguish between structures at the telomeric overhang and those forming in the normally double-stranded region of telomeres.…”

Section: G-quadruplexes In the Telomeric Single-stranded Overhangmentioning

confidence: 99%

G-Quadruplexes at Telomeres: Friend or Foe?

Bryan

2020

Molecules

126

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Telomeres are DNA-protein complexes that cap and protect the ends of linear chromosomes. In almost all species, telomeric DNA has a G/C strand bias, and the short tandem repeats of the G-rich strand have the capacity to form into secondary structures in vitro, such as four-stranded G-quadruplexes. This has long prompted speculation that G-quadruplexes play a positive role in telomere biology, resulting in selection for G-rich tandem telomere repeats during evolution. There is some evidence that G-quadruplexes at telomeres may play a protective capping role, at least in yeast, and that they may positively affect telomere maintenance by either the enzyme telomerase or by recombination-based mechanisms. On the other hand, G-quadruplex formation in telomeric DNA, as elsewhere in the genome, can form an impediment to DNA replication and a source of genome instability. This review summarizes recent evidence for the in vivo existence of G-quadruplexes at telomeres, with a focus on human telomeres, and highlights some of the many unanswered questions regarding the location, form, and functions of these structures.

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Section: G-quadruplexes In the Telomeric Single-stranded Overhangmentioning

confidence: 99%

G-Quadruplexes at Telomeres: Friend or Foe?

Bryan

2020

Molecules

126

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“…Actually, ap19 turned out to be a pure hybrid-2 type fold and the ap7 a hybrid-1 architecture, although the latter formed clearly only at high, millimolar strand concentrations. Folding topology of the wild-type htel-21 and A(htel-21) GQs has been found to depend on the oligonucleotide strand concentrations and to change qualitatively above 2 mM of strands [ 310 – 313 ]. Polymorphism increased when the A/AP was located in the middle loop at position 13, and this was the ap13 structure(s).…”

Section: Natural Base Lesions and Epigenetic Modifications In Gq Dmentioning

confidence: 99%

“…At high concentration, 200 mM, of KCl, this loop-abasic GQ formed higher-order aggregates, that is, short nanowires of ~20 nm length, that were long G4-stacks [ 316 ]. The loop-abasic sites have been used in several other GQ model studies, such as in the ribo analog of the telomeric DNA and TERRA [ 169 ] and also with A(htel-21) [ 313 ]. Heddi et al [ 317 ] investigated the formation of GQs containing 4n-1 guanines in the core and synthesized, among others, the T 2 G G GT(G 3 T) 3 oligodeoxynucleotide, where the G is for the G/AP site in the middle tetrad of the three-tetrad GQ.…”

Section: Natural Base Lesions and Epigenetic Modifications In Gq Dmentioning

confidence: 99%

In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?

Sági¹

2017

Journal of Nucleic Acids

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Synthetic analogs of natural nucleotides have long been utilized for structural studies of canonical and noncanonical nucleic acids, including the extensively investigated polymorphic G-quadruplexes (GQs). Dependence on the sequence and nucleotide modifications of the folding landscape of GQs has been reviewed by several recent studies. Here, an overview is compiled on the thermodynamic stability of the modified GQ folds and on how the stereochemical preferences of more than 70 synthetic and natural derivatives of nucleotides substituting for natural ones determine the stability as well as the conformation. Groups of nucleotide analogs only stabilize or only destabilize the GQ, while the majority of analogs alter the GQ stability in both ways. This depends on the preferred syn or anti N-glycosidic linkage of the modified building blocks, the position of substitution, and the folding architecture of the native GQ. Natural base lesions and epigenetic modifications of GQs explored so far also stabilize or destabilize the GQ assemblies. Learning the effect of synthetic nucleotide analogs on the stability of GQs can assist in engineering a required stable GQ topology, and exploring the in vitro action of the single and clustered natural base damage on GQ architectures may provide indications for the cellular events.

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“…In contrast, CCCCGG repeats did not form phase transitions, suggesting that not all xtrRNA will possess these properties. Interestingly, guanine-rich nucleic acids are less soluble than other nucleic acids and appear to be intrinsically aggregate-prone apart from protein, especially when packing into quartets or higher-order quadruplex structures [21, 89, 179]. The disruption of membrane-free organelles, which are abundant in the nucleus, is linked to disease [198, 228, 272].…”

Section: Structure Protein Interactions and Localization Of Xtrrnamentioning

confidence: 99%

RNA biology of disease-associated microsatellite repeat expansions

Rohilla

Gagnon

2017

acta neuropathol commun

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Microsatellites, or simple tandem repeat sequences, occur naturally in the human genome and have important roles in genome evolution and function. However, the expansion of microsatellites is associated with over two dozen neurological diseases. A common denominator among the majority of these disorders is the expression of expanded tandem repeat-containing RNA, referred to as xtrRNA in this review, which can mediate molecular disease pathology in multiple ways. This review focuses on the potential impact that simple tandem repeat expansions can have on the biology and metabolism of RNA that contain them and underscores important gaps in understanding. Merging the molecular biology of repeat expansion disorders with the current understanding of RNA biology, including splicing, transcription, transport, turnover and translation, will help clarify mechanisms of disease and improve therapeutic development.

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Concentration-dependent conformational changes in GQ-forming ODNs

Cited by 10 publications

References 21 publications

G-Quadruplexes at Telomeres: Friend or Foe?

G-Quadruplexes at Telomeres: Friend or Foe?

In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?

RNA biology of disease-associated microsatellite repeat expansions

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