Formation of a hairpin structure by telomere 3′ overhang

Choi, Ki Hang; Choi, Byung-Seok

doi:10.1016/0167-4781(94)90298-4

Cited by 19 publications

(18 citation statements)

References 23 publications

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“…This was the best way to stabilize homoduplexes and simultaneously avoid tetraplexes. 33 We found that the homoduplexes arose in a cooperative way, which was interesting, because the homoduplexes contained no WatsonCrick basepairs. The midpoints of the transitions shifted towards higher salt concentrations with the increasing adenine content, while the limiting spectra were almost the same for all the d(G+A) n homoduplexes at 0°C (Fig.…”

Section: Discussionmentioning

confidence: 97%

Circular dichroism spectroscopy of conformers of (guanine + adenine) repeat strands of DNA

2003

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(Guanine+adenine) strands of DNA are known to associate into guanine tetraplexes, homodimerize into parallel or antiparallel duplexes, and fold into a cooperatively melting single strand resembling the protein alpha helix. Using CD spectroscopy and other methods, we studied how this conformational polymorphism depended on the primary structure of DNA. The study showed that d(GGGA)(5) and d(GGA)(7) associated into homoduplexes at low salt or in the presence of LiCl but were prone to guanine tetraplex formation, especially in the presence of KCl. In addition, they yielded essentially the same CD spectrum in the presence of ethanol as observed with the ordered single strand of d(GA)(10). Strands of d(GA)(10), d(GGAA)(5), d(GAA)(7), and d(GAAA)(5) associated into homoduplexes in both LiCl and KCl solutions, but not into guanine tetraplexes. d(GAAA)(5) and d(GAA)(7) further failed to form the single-stranded conformer in aqueous ethanol. Adenine protonation, however, stabilized the single-stranded conformer even in these adenine-rich fragments. The ordered single strands, homoduplexes as well as the guanine tetraplexes, all provided strikingly similar CD spectra, indicating that all of the conformers shared similar base stacking geometries. The increasing adenine content only decreased the conformer thermostability.

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Section: Discussionmentioning

confidence: 97%

Circular dichroism spectroscopy of conformers of (guanine + adenine) repeat strands of DNA

2003

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“…This is understandable because DNA is a polyanion and cations should screen repulsion of DNA phosphates for the DNA strands to come close to each other in the tetraplex. However guanine tetraplexes are remarkably specific with respect to the cation type because Li þ does not stabilize guanine tetraplexes 22 while, e.g., K þ , Pb 2þ , or Sr 2þ do so very efficiently. 1,42 Hence there are sites in the guanine tetraplexes at which cations bind selectively.…”

Section: Discussionmentioning

confidence: 98%

“…A simple G.G reverse Hoogsteen base pairing was observed, e.g., in LiCl. 22 Higher ethanol concentrations induce the parallel tetraplexes with a long kinetics. The additional small positive band at 295 nm indicates a presence of still other aggregates.…”

Section: Methodsmentioning

confidence: 99%

Ethanol is a better inducer of DNA guanine tetraplexes than potassium cations

Vorlı́čková¹,

Bednářová²,

Kypr³

2006

Biopolymers

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Guanine tetraplexes are a biologically relevant alternative of the Watson and Crick duplex of DNA. It is thought that potassium or other cations present in the cavity between consecutive guanine tetrads are an integral part of the tetraplexes. Here we show using CD spectroscopy that ethanol induces the guanine tetraplexes like or even better than potassium cations. We present examples of ethanol stabilizing guanine tetraplexes even in cases when potassium cations fail to do so. Hence, besides the A-form or Z-form, ethanol stabilizes another conformation of DNA, i.e., the guanine tetraplexes. We discuss the mechanism of the stabilization. Use of ethanol will permit studies of guanine tetraplexes that cannot be induced by potassium cations or other tetraplex-promoting agents. This work demonstrates that a still broader spectrum of nucleotide sequences can fold into guanine tetraplexes than has previously been thought. Aqueous ethanol may better simulate conditions existing in vivo than the aqueous solutions.

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“…7), and thus it appears that these oligomers also maintain a hairpin structure rather than a tetraplex conformation. The weight of the evidence provided here points, therefore, at a similarity between the d(CGG) n tracts and telomeric DNA sequences, which are capable of forming back-folded hairpin structures at a physiological range of salt concentrations, temperatures and pH values (Sundquist and Klug, 1989;Sen and Gilbert, 1990;Balagurumoorthy and Brahmachari, 1994;Choi and Choi, 1994).…”

Section: Discussionmentioning

confidence: 99%

The Fragile X Syndrome Single Strand d(CGG)n Nucleotide Repeats Readily Fold Back to Form Unimolecular Hairpin Structures

Nadel¹,

Weisman-Shomer²,

Fry³

1995

Journal of Biological Chemistry

108

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Expansion of a d(CGG)nFragile X syndrome is an inherited, X-linked dominant mental retardation disorder affecting about one male in 1500 and one female in 2500 (Webb, 1989;Richards and Sutherland, 1992). This syndrome is frequently associated with a folatesensitive fragile site, Xq27.3, on chromosome X of cells of affected males (Sutherland, 1977). The fragile X syndrome is characterized by a substantial expansion of a d(CGG) trinucleotide repeat located in the 5Ј-untranslated region of a housekeeping gene, FMR1, which was identified at a locus coincident with the Xq27.3 breakpoint (Verkek et al., 1991). Whereas normal individuals have 2-50 copies of the d(CGG) sequence, the trinucleotide is amplified in affected subjects to Ͼ200 -2000 copies Kremer et al., 1991;Oberlé et al., 1991; Nakhahori et al., 1991; Verkek et al., 1991;Yu et al., 1991). Expansion of the d(CGG) repeat is accompanied by methylation of the FMR1 promoter and of the amplified trinucleotide tract (Bell et al., 1991;Vincent et al., 1991;Pieretti et al., 1991;Luo et al., 1993). Subsequent to d(CGG) expansion and hypermethylation, the FMR1 gene becomes transcriptionally silent Hansen et al., 1992;Sutcliffe et al., 1992), and the replication of a chromosomal segment spanning Ն150 kb 5Ј and Ն34 kb 3Ј from the d(CGG) n stretch is delayed (Hansen et al., 1993).The molecular mechanisms that govern d(CGG) n amplification and hypermethylation and that link d(CGG) expansion to the suppressed transcription of FMR1 and to its delayed replication are not known. In addressing these problems, we showed recently that model d(CGG) n oligomers form under physiological conditions a tetramolecular four-stranded structure in a time-dependent and DNA concentration-dependent kinetics. We also found that the multimolecular tetraplex structure of short d(CGG) n tracts is stabilized by 5-methylation of the cytosine residues (Fry and Loeb, 1994). The facile formation of tetramolecular complexes by d(CGG) n raised the hypothesis that single stranded stretches of this tract may also generate unimolecular hairpin or tetraplex structures (Fry and Loeb, 1994). In this communication we use gel mobility analysis and chemical probing to demonstrate that d(CGG) n oligodeoxynucleotides can fold back at a physiological range of salt concentrations, temperatures, and pH values to form hairpin structures. In contrast to the second-order kinetics of formation of tetramolecular quadruplex d(CGG) n (Fry and Loeb, 1994), hairpin structures of this sequence are formed at a zero-order kinetics. Our evidence for hairpin formation by d(CGG) n is sustained by reports by Gacy et al. (1995) and Chen et al. (1995), which were published as this work was completed and that provide NMR evidence to also show the formation of hairpin structures by d(CGG) n and by other trinucleotide tracts.The folding of exposed expanded single strand runs of d(CGG) n during the replication of fragile X cell DNA could entail slippage and trinucleotide expansion. Furthermore, guanine-rich tracts of RNA or DNA that fol...

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Formation of a hairpin structure by telomere 3′ overhang

Cited by 19 publications

References 23 publications

Circular dichroism spectroscopy of conformers of (guanine + adenine) repeat strands of DNA

Circular dichroism spectroscopy of conformers of (guanine + adenine) repeat strands of DNA

Ethanol is a better inducer of DNA guanine tetraplexes than potassium cations

The Fragile X Syndrome Single Strand d(CGG)n Nucleotide Repeats Readily Fold Back to Form Unimolecular Hairpin Structures

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