Alkali metal ion specificity in the solution ordering of a nucleotide, 5'-guanosine monophosphate

Pinnavaia, T. J.; Marshall, Christopher L.; Mettler, Claudia M.; Fisk, Cherie L.; Miles, H. Todd; Becker, Edwin D.

doi:10.1021/ja00479a070

Cited by 201 publications

(203 citation statements)

References 2 publications

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“…1, is based on the ability of such sequences to block DNA polymerase progression in the presence of K ϩ but not in the absence of monovalent cations or in the presence of cations such as Li ϩ , NH 4 ϩ , Rb ϩ , or Cs ϩ . The specificity of this reaction for K ϩ is probably related to the fact that its ionic radius is small enough for the ion to fit inside the tetraplex cavity but is still large enough for it to interact with the keto oxygens of guanines in adjacent tetrads (41). This K ϩ specificity parallels the K ϩ -dependent anomalous mobility of tetraplex-forming oligonucleotides that is considered a diagnostic feature of tetraplex formation (35,42,43).…”

Section: Resultsmentioning

confidence: 87%

“…This interpretation is consistent with the fact that other monovalent cations such as Rb ϩ , Cs ϩ , and NH 4 ϩ do not result in a block to DNA synthesis in our assay, since these ions have radii that are all larger than that of K ϩ . Li ϩ , on the other hand, is much smaller than Na ϩ and may still be too small to form the coordination complex that is important in stabilizing these types of structures (41). Our assay might thus be useful in distinguishing between different kinds of tetraplexes such as those that are K ϩ -specific and that correspond to previously described G 4 tetrad containing tetraplexes and those that are also seen in the presence of other cations, specifically Na ϩ , that may represent a novel class of tetraplex with different base interactions and thus different properties.…”

Section: Discussionmentioning

confidence: 99%

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DNA Secondary Structures and the Evolution of Hypervariable Tandem Arrays

Woodford

Usdin

Weitzmann

1997

Journal of Biological Chemistry

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Tandem repeats are ubiquitous in nature and constitute a major source of genetic variability in populations. This variability is associated with a number of genetic disorders in humans including triplet expansion diseases such as Fragile X syndrome and Huntington's disease. The mechanism responsible for the variability/instability of these tandem arrays remains contentious. We show here that formation of secondary structures, in particular intrastrand tetraplexes, is an intrinsic property of some of the more unstable arrays. Tetraplexes block DNA polymerase progression and may promote instability of tandem arrays by increasing the likelihood of reiterative strand slippage. In the course of doing this work we have shown that some of these tetraplexes involve unusual base interactions. These interactions not only generate tetraplexes with novel properties but also lead us to conclude that the number of sequences that can form stable tetraplexes might be much larger than previously thought.

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Section: Resultsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

DNA Secondary Structures and the Evolution of Hypervariable Tandem Arrays

Woodford

Usdin

Weitzmann

1997

Journal of Biological Chemistry

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“…K ϩ ions are generally the most effective monovalent cations at stabilizing these structures. It is thought that this is due either to an optimal fit of K ϩ inside the stem of the tetraplexes such that the cation is able to coordinate the O 6 atoms of guanines in adjacent tetrads (18) or to its relative ease of dehydration (19). We have recently demonstrated that the ability to block DNA synthesis in the presence of K ϩ is a diagnostic feature of intrastrand tetraplexes (11), presumably because the K ϩ -stabilized tetraplexes form a barrier to polymerase progression.…”

Section: Resultsmentioning

confidence: 99%

The Mouse Ms6-hm Hypervariable Microsatellite Forms a Hairpin and Two Unusual Tetraplexes

Weitzmann

Woodford

Usdin

1998

Journal of Biological Chemistry

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The mouse Ms6-hm microsatellite consists of a tandem array of the pentamer d(CAGGG) n . This microsatellite is extremely hypervariable, showing a germ line mutation rate of 2.5%/gamete. The mechanism responsible for this instability is not known. The ability to form intrastrand structures is a conserved feature of many hypervariable sequences, and it has been suggested that the formation of such structures might account for instability by affecting DNA replication, repair, or recombination. Here we show that this microsatellite is able to form intrastrand structures as well. Under physiological conditions, the Ms6-hm microsatellite forms a hairpin as well as two different unusual intrastrand tetraplexes. The hairpin forms in the absence of monovalent cation and contains G⅐A, G⅐C, and G⅐G base pairs in a 1:1:1 ratio. In the presence of K ؉ , a tetraplex is formed in which the adenines are unpaired and extrahelical, and the cytosines are involved in C⅐C pairs. In Na ؉ , a tetraplex forms that contains C⅐C ؉ pairs, with the adenines being intrahelical and hydrogen-bonded to guanines. Tetraplex formation in the presence of Na ؉ requires both cytosines and adenines and might reflect the altered internal dimensions of this tetraplex, perhaps resulting from the ability of the C⅐C ؉ pairs to become intercalated in this sequence context. Our demonstration of the stabilization of tetraplexes by hydrogen bonding between adenines and guanines expands the hydrogen-bonding possibilities for tetraplexes and suggests that the category of sequences with tetraplex-forming potential may be larger than previously appreciated.

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“…Such Gquartet pairing alignments have been observed and characterized in systems ranging from guanine monophosphates (Pinnavaia, Miles & Becker, 1975;Pinnavaia et al, 1978;Borzo, Detellier, Lazlo & Paris, 1980) to , (~ 1996 International Union of Crystallography Printed in Great Britain -all rights reserved polyguanylic acid (Gellert, Lipsett & Davies, 1962). More recent interest has been in the direction of higher order structures adopted by single-stranded telomeric overhangs at the ends of chromosomes (Blackburn & Szostak, 1984;Blackburn, 1991).…”

Section: Introductionmentioning

confidence: 99%

An Ambiguous Structure of a DNA 15-mer Thrombin Complex

Padmanabhan

Tulinsky²

1996

Acta Crystallogr D Biol Crystallogr

168

194

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The structure of a complex between thrombin and a GGTTGGTGTGGTTGG DNA 15-mer has been analyzed crystallographically. The solution NMR structure of the 15-mer has two stacked G-quartets similar to that found in the previous X-ray structure determination of the 15-mer-thrombin complex [Padmanabhan, Padmanabhan, Ferrara, Sadler & Tulinsky (1993). J. Biol. Chem. 268, 17651-17654]; the strand polarity, however, is reversed from that of the crystallographic structure. The structure of the complex here has been redetermined with better diffraction data confirming the previous crystallographic structure but also indicating that the NMR solution structure fits equally well. Both 15-mer complex structures refined to an R value of about 0.16 presenting a disconcerting ambiguity. Since the two 15-mer structures associate with thrombin in different ways (through the TGT loop in the X-ray and TT loop in the NMR model), other independent lines of physical or chemical evidence are required to resolve the ambiguity.

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Alkali metal ion specificity in the solution ordering of a nucleotide, 5'-guanosine monophosphate

Cited by 201 publications

References 2 publications

DNA Secondary Structures and the Evolution of Hypervariable Tandem Arrays

DNA Secondary Structures and the Evolution of Hypervariable Tandem Arrays

The Mouse Ms6-hm Hypervariable Microsatellite Forms a Hairpin and Two Unusual Tetraplexes

An Ambiguous Structure of a DNA 15-mer Thrombin Complex

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