Solution structure of the human telomeric repeat d[AG3(T2AG3)3] G-tetraplex

Wang, Yong; Patel, Dinshaw J.

doi:10.1016/0969-2126(93)90015-9

Cited by 1,343 publications

(1,568 citation statements)

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“…8,11 The DNA samples (~7 mL) were first dialyzed against water, then against 150 mM NaCl, 10 mM sodium phosphate buffer (pH 6.8), and finally against 15 mM NaCl, 0.2 mM sodium phosphate buffer (pH 6.6) and lyophilized. Unless otherwise stated, the strand concentration of the NMR samples was typically 0.5-5 mM; the solutions contained 100 mM NaCl and 10 mM sodium phosphate (pH 6.8).…”

Section: Sample Preparationmentioning

confidence: 99%

“…Crystal structure of the nearly four-repeat human telomeric d(AG 3 (TTAGGG) 3 ) sequence in the presence of K + represents a monomeric (intramolecular) parallel-stranded G-quadruplex with anti guanines and double-chainreversal loops. 6 In contrast, the same sequence forms in Na + solution a different intramolecular G-quadruplex, 8 where guanines around each tetrad are syn·syn·anti·anti, loops are successively edgewise-diagonal-edgewise and each G-tract has both a parallel and an antiparallel adjacent strands (Figure 1b). Interestingly, the Tetrahymena telomeric sequences, which differ from the human counterparts only by one G-for-A replacement in each repeat, form totally different G-quadruplex topologies in Na + solution.…”

Section: Introductionmentioning

confidence: 99%

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(3 + 1) Assembly of Three Human Telomeric Repeats into an Asymmetric Dimeric G-Quadruplex

2005

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We present an NMR study on the structure of a DNA fragment of the human telomere containing three guanine-tracts, d(GGGTTAGGGTTAGGGT). This sequence forms in Na + solution a unique asymmetric dimeric quadruplex, in which the G-tetrad core involves all three G-tracts of one strand and only the last 3′-end G-tract of the other strand. We show that a three-repeat human telomeric sequence can also associate with a single-repeat human telomeric sequence into a structure with the same topology that we name (3 + 1) quadruplex assembly. In this G-quadruplex assembly, there are one syn·syn·syn·anti and two anti· anti·anti·syn G-tetrads, two edgewise loops, three G-tracts oriented in one direction and the fourth oriented in the opposite direction. We discuss the possible implications of the new folding topology for understanding the structure of telomeric DNA, including t-loop formation, and for targeting G-quadruplexes in the telomeres.

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Section: Sample Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

(3 + 1) Assembly of Three Human Telomeric Repeats into an Asymmetric Dimeric G-Quadruplex

2005

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“…To confirm this observation, we performed a UV-visible titration of cryptolepine (10 µM) with increasing amounts of 22 AG (0-12 µM). This oligonucleotide mimics the repeats of the human telomeric motif, and may adopt an intramolecular quadruplex structure [42,43]. This titration was performed in the presence of 0.1 M KC1, i.e.…”

Section: Quadruplex Bindingmentioning

confidence: 99%

Interactions of cryptolepine and neocryptolepine with unusual DNA structures

et al. 2003

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1 These authors contributed equally to this work. AbstractCryptolepine, the main alkaloid present in the roots of Cryptolepis sanguinolenta, presents a large spectrum of biological properties. It has been reported to behave like a DNA intercalator with a preference for GC-rich sequences. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of cryptolepine and neocryptolepine for DNA structures among duplexes, triplexes, quadruplexes and single strands. Our data confirm that cryptolepine and neocryptolepine prefer GC over AT-rich duplex sequences, but also recognize triplex and quadruplex structures. These compounds are weak telomerase inhibitors and exhibit a significant preference for triplexes over quadruplexes or duplexes.

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“…DNA; 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].…”

Section: Introductionmentioning

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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Solution structure of the human telomeric repeat d[AG3(T2AG3)3] G-tetraplex

Cited by 1,343 publications

References 39 publications

(3 + 1) Assembly of Three Human Telomeric Repeats into an Asymmetric Dimeric G-Quadruplex

(3 + 1) Assembly of Three Human Telomeric Repeats into an Asymmetric Dimeric G-Quadruplex

Interactions of cryptolepine and neocryptolepine with unusual DNA structures

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

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