The new models of the human telomere d[AGGG(TTAGGG)3] in K+ solution

Xu, Yan; Noguchi, Yuki; Sugiyama, Hiroshi

doi:10.1016/j.bmc.2006.04.033

Cited by 367 publications

(401 citation statements)

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“…Numerous studies have shown that the circular dichroism (CD) technique is sensitive to the strand arrangement°in°DNA°quadruplexes° [9 -11,°18,°32-40].°For example, Vorlíčková et al studied various topologies of the quadruplexes formed by the human telomere DNA fragments G 3 (TTAG 3 ) n ,°where°n ϭ°1-16° [39].°Xu°et°al., using the CD technique, examined the quadruplex structure generated by the human telomeric sequence d[AGGG(TTAGGG) 3 ] by substituting the G's with 8-bromoguanine° [36];°this°structure°had°been°controver-sial for a long time. They proposed that the 22 nt in K ϩ forms a mixture of mixed-parallel/antiparallel and chair-type quadruplexes.…”

Section: Spectra Of the Bimolecular And Higher-order Speciesmentioning

confidence: 99%

“…As an intermediate, the bimolecular structure can°vary°from°one°form°to°another° [30] 2 and unfold the structure; the strands then rearrange alignment in the denatured state and pair with other strands to form more stable parallel structures° [32].°Xu°et°al.°indicate°a°possible°shift°be-tween the mixed-parallel/antiparallel and the chairtype quadruplexes formed by the human telomere sequence°in°K ϩ°i on°solution° [36].°In°the°present°work, we show that two of the four bimolecular quadruplexes are not terminal products and are converted to more stable structures. The transition rates probably depend on the stabilities and specific structures of the bimolecular quadruplexes, as well as on the solution conditions.…”

Section: Spectra Of the Bimolecular And Higher-order Speciesmentioning

confidence: 99%

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Bimolecular quadruplexes and their transitions to higher-order molecular structures detected by ESI-FTICR-MS

Guo

Liu

2007

J. Am. Soc. Mass Spectrom.

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Four individual quadruplexes, which are self-assembled in ammonium acetate solution from telomeric sequences of closely related DNA strands-d(G 4 T 4 G 4 ), d(G 3 T 4 G 4 ), d(G 3 T 4 G 3 ), and d(G 4 T 4 G 3 )-have been detected in the gas phase using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS). The bimolecular quadruplexes associate with the same number of NH 4 ϩ in the gas phase as NMR shows that they do in solution. The quadruplex structures formed in solution are maintained in the gas phase. Furthermore, the mass spectra show that the bimolecular quadruplexes generated by the strands d( Of particular interest is a telomeric DNA that consists of repeating sequences, such as TTAGGG in vertebrates and TTTTGGGG in Oxytricha. These sequences have been proven to fold into quadruplexes in vitro and potentially have the function of inhibiting telomerase activities. The telomerase, a reverse enzyme expressed in more than 80% of tumor cells, responds for the replication of the telomeric DNA and has been considered as a target for anticancer drug design [4,5]. Guanine-rich oligonucleotides can also self-associate into higher-order structures, such as supermolecular G-wires [6], which serve as artificial ion channels and ion receptors and which have a wide range of applications in medicine, materials science, and nanotechnology [2,7,8].DNA quadruplex structures can be formed from one, two, or four oligonucleotide strands and are stabilized by coordinated monovalent cations acting between adjacent G-quartets [1, 9 -11]. The strands with single repeating guanine sequences usually arrange themselves from the 5= to the 3= end in parallel four-stranded quadruplexes, whereas the strands with more than two tracks of repeating guanine units can form a number of quadruplexes that are distinguished by their strand number, strand orientation, and loop types. The structural topologies of DNA quadruplexes also drastically change with slight changes of the DNA sequences, with the nature of the cationic species and with their concentrations in solution. As a result, the structures of DNA quadruplexes are far from being fully recognized and have been of concern to researchers because of their potential implications in biological and structural applications.Development in electrospray ionization mass spectrometry (ESI-MS) has been shown to be superior in the analysis of DNA noncovalent complexes in terms of speed, sensitivity, stoichiometry, and specificity compared to other analytical techniques [12]. Previous work by ourselves and others have shown that some specific DNA conformations, such as hairpins, triplexes, and quadruplexes formed in solution, can survive in the gas phase [13][14][15][16][17][18][19][20]. This prompted us to explore the structural properties of DNA quadruplexes with ESI-MS so as to add new information concerning them.

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Section: Spectra Of the Bimolecular And Higher-order Speciesmentioning

confidence: 99%

Section: Spectra Of the Bimolecular And Higher-order Speciesmentioning

confidence: 99%

Bimolecular quadruplexes and their transitions to higher-order molecular structures detected by ESI-FTICR-MS

Guo

Liu

2007

J. Am. Soc. Mass Spectrom.

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“…The diffusion coefficients of both peaks are very similar to that of Tel22-Mut. Tel22 in K + solution forms a mixture of two unimolecular conformations ( Figure S3B) [5,7,64], whose folding and consequently the overall shapes are different, which may correspond to the two slightly different projection peaks. The MS analysis of the Tel22 sample showed no higher or lower molecular weights present in this sample (data not shown).…”

Section: Human Telomeric Wild-type G-quadruplexesmentioning

confidence: 99%

Diffusion-ordered nuclear magnetic resonance spectroscopy for analysis of DNA secondary structural elements

Ambrus¹,

Yang²

2007

Analytical Biochemistry

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Structure determination of secondary DNA structural elements, such as G-quadruplexes, gains an increasing importance as fundamental physiological roles are being associated with the formation of such structures in vivo. A truncated native DNA sequence generally requires further optimization to obtain a candidate with desired NMR properties for structural analysis in solution. The optimum sequence is expected to form one dominant, stable molecular entity in solution with well-resolved NMR peaks. However, DNA sequences are prone to form structures composed of one, two, three or four strands depending on sequence and solution conditions. The thorough characterization of the molecularity (stoichiometry and molecular weight) and appropriate solution conditions for sequences with different modifications traditionally applies analytical techniques that generally do not represent the solution conditions for NMR structure determination. Here we present the application of diffusion ordered NMR spectroscopy as a useful analytical tool for the optimization and analysis of DNA secondary structural elements, specifically, the DNA G-quadruplex structures, including those formed in the human telomeric sequence and in the promoter regions of bcl-2 and c-myc genes. KeywordsDNA; NMR; DOSY; quadruplex; bcl-2; human telomere; c-myc Structural analysis of unusual DNA motifs with particular emphasis on G-quadruplexes and imotifs has a central role in the identification and characterization of molecular targets related to these structures [1][2][3][4][5][6][7]. Such structures are implicated in several physiologically important regulatory processes, with special emphasis on carcinogenesis [4][5][6][7][8][9][10][11][12]. Most of the structural studies on these elements have been performed by NMR spectroscopy. In most cases the related nucleotide sequence bearing the actual physiological function in vivo needs to be truncated/ elongated and/or mutated in order to obtain a successful candidate for NMR structure determination [3][4][5][6][7]13]. This NMR candidate should be a well-defined molecular entity in physiologically relevant solution conditions (ionic strength, pH, temperature) representing the same conformation as the original sequence. Appropriate modification of the sequence by mutation/truncation/elongation will force the molecule to form a single stable structure without altering crucial connectivities (conformation) of the structure.* To whom correspondence should be addressed at the Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 E. Mabel St., P.O. Box 210207, room 101/406, Tucson, Arizona 85721, USA; Tel: +1 520 626 6749/626 5969, Fax: +1 520 626 2466, E-mail: ambrus@pharmacy.arizona.edu, yangd@pharmacy.arizona.edu.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of ...

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“…Of particular interest recently are the conformations available to G-rich DNAs which are designated as G-quadruplexes. DNA sequences that have islands of G 2-4 separated by 1 to 4 A and/or T bases can form a rich library of secondary structures with different molecularities, strand orientations, and guanine base conformation (i.e., syn or anti) [3][4][5][6][7][8][9][10][11][12][13][14]. The conformations and their stabilities are highly dependent upon the sequence context and buffer conditions [15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

The Human Telomere Sequence, (TTAGGG)4, in the Absence and Presence of Cosolutes: A Spectroscopic Investigation

Sharma

Sheardy

2014

Molecules

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Abstract:Historically, biophysical studies of nucleic acids have been carried out under near ideal conditions, i.e., low buffer concentration (e.g., 10 mM phosphate), pH 7, low ionic strength (e.g., 100 mM) and, for optical studies, low concentrations of DNA (e.g., 1 × 10 −6 M). Although valuable structural and thermodynamic data have come out of these studies, the conditions, for the most, part, are inadequate to simulate realistic cellular conditions. The increasing interest in studying biomolecules under more cellular-like conditions prompted us to investigate the effect of osmotic stress on the structural and thermodynamic properties of DNA oligomers containing the human telomere sequence (TTAGGG). Here, we report the characterization of (TTAGGG) 4 in potassium phosphate buffer with increasing percent PEG (polyethylene glycol) or acetonitrile. In general, the presence of these cosolutes induces a conformational change from a unimolecular hybrid structure to a multimolecular parallel stranded structure. Hence, the structural change is accompanied with a change in the molecularity of quadruplex formation.

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The new models of the human telomere d[AGGG(TTAGGG)3] in K+ solution

Cited by 367 publications

References 48 publications

Bimolecular quadruplexes and their transitions to higher-order molecular structures detected by ESI-FTICR-MS

Bimolecular quadruplexes and their transitions to higher-order molecular structures detected by ESI-FTICR-MS

Diffusion-ordered nuclear magnetic resonance spectroscopy for analysis of DNA secondary structural elements

The Human Telomere Sequence, (TTAGGG)4, in the Absence and Presence of Cosolutes: A Spectroscopic Investigation

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