On the Relative Ability of Centromeric GNA Triplets to Form HairpinsversusSelf-paired Duplexes

Chou, Shan‐Ho; Zhu, Lianjie; Reid, Brian R.

doi:10.1006/jmbi.1996.0331

Cited by 36 publications

(38 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SC also reveals that the amino protons of the two unpaired guanines 4G and 14G (small yellow spheres) are very likely to be involved in hydrogen bonding to the opposite-strand phosphate oxygens of 15A and 5A (small magenta spheres), respectively. Even though there is no direct experimental evidence for this hydrogen bond, which arose spontaneously during the embedding and refining process, its proposed stabilization effect nicely explains our observation that the (GGA)2 motif is more stable in a duplex than the analogous (GAA)2 motif-the latter forming a hairpin-duplex equilibrium containing predominantly hairpin in most sequence contexts (9).…”

Section: Structural Featuressupporting

confidence: 57%

“…The most frequent among these variants is TGCAA-i.e., the central GGA triplet [which forms the self-paired (GGA)2 motifl is changed to GCA. Interestingly, we recently found that the triplet GCA is a very strong hairpin promoter (8,9). Among the four GNA triplets in a d(NAATGNAATG) sequence context, GGA predominantly forms bimolecular duplexes containing a (GGA)2 motif, as described previously (3,4), while GCA forms a unimolecular hairpin (8,9) and GAA and GTA form a mixture of mostly hairpin in equilibrium with a minor (GNA)2 duplex form (9).…”

supporting

confidence: 60%

“…Interestingly, in our earlier systematic studies of GNA triplets in the sequence context d(NAATGNAATG), where N is G, A, T, or C (9), it was found that the Hi' chemical shift and the sugar conformation of the N residue are important and diagnostic criteria that can be used to distinguish between the (GNA) hairpin loop motif and the bimolecular duplex (GNA)2 motif. In the (GNA)2 duplex pairing motif, the Hi' resonance of the N residue is shifted upfield and its sugar is in the unusual C3'-endo conformation, while in the (GNA)-turn loop motif, the Hi' resonance of the N residue is not shifted upfield and its sugar is in the normal C2'-endo conformation (9). In the present case the C3'-endo sugar conformation for residues 4G and 14G is further confirmed by DQF-COSY experiments (see below).…”

Section: Spectral Analysismentioning

confidence: 97%

“…Interestingly, we recently found that the triplet GCA is a very strong hairpin promoter (8,9). Among the four GNA triplets in a d(NAATGNAATG) sequence context, GGA predominantly forms bimolecular duplexes containing a (GGA)2 motif, as described previously (3,4), while GCA forms a unimolecular hairpin (8,9) and GAA and GTA form a mixture of mostly hairpin in equilibrium with a minor (GNA)2 duplex form (9). If (TGGAA), repeats self-pair to form antiparallel (GGA)2 motifs in vivo, we reasoned that occasional TGCAA pentamers interspersed among (TG-GAA), repeats might promote folding back of the chain on itself by forming GCA-turn loops, and thus modulate centromere folding.…”

mentioning

confidence: 99%

See 3 more Smart Citations

A single G-to-C change causes human centromere TGGAA repeats to fold back into hairpins.

Zhu

Chou

Reid

1996

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Recently, we established that satellite III (TGGAA). tandem repeats, which occur at the centromeres of human chromosomes, pair with themselves to form an unusual "self-complementary" antiparallel duplex containing (GGA)2 motifs in which two unpaired guanines from opposite strands intercalate between sheared GoA base pairs. In separate studies, we have also established that the GCA triplet does not form bimolecular (GCA)2 motifs but instead promotes the formation of hairpins containing a GCA-turn motif in which the loop contains a single cytidine closed by a sheared GoA pair. Since TGCAA is the most frequent variant of TGGAA found in satellite III repeats, we reasoned that the potential of this variant to form GCA-turn miniloop fold-back structures might be an important factor in modulating the local structure in natural (TGGAA The classical satellite III of human DNA, which has been located in the centromere region of chromosomes (1), is composed of (TGGAA)n repeats with the consensus sequence 5'-CAACCCGAM(TGGAA), (2). From the cooperative UVmelting transition Grady et al. (1) found that, in the absence of the complementary TTCCA strand, (TGGAA)6 alone can somehow pair with itself to form a stable duplex with a Tm of 65°C. We recently solved the solution structure of the antiparallel "self-complementary" (TGGAATGGAA)2 duplex containing a tandem TGGAA repeat; this structure contains two (GGA)2 motifs in which the central guanines from opposite strands are unpaired and intercalatively stacked on each other between flanking GoA pairs (3, 4). The flanking G°A pairs are in the sheared, or side-by-side, configuration (5-7) and the guanines of the (GGA)2 motif form a four-guanine interstrand stack. Although the (TGGAA)n repeat is highly conserved in satellite III, perfect repeats rarely continue for more than 12-15 repeats (60-75 bp) with several variants that differ from the consensus pentamer by only a single base. The most frequent among these variants is TGCAA-i.e., the central GGA triplet [which forms the self-paired (GGA)2 motifl is changed to GCA. Interestingly, we recently found that the triplet GCA is a very strong hairpin promoter (8, 9). Among the four GNA triplets in a d(NAATGNAATG) sequence context, GGA predominantly forms bimolecular duplexes containing a (GGA)2 motif, as described previously (3, 4), while GCA forms a unimolecular hairpin (8, 9) and GAA and GTA form a mixture of mostly hairpin in equilibrium with a minor (GNA)2 duplex form (9). If (TGGAA), repeats self-pair to form antiparallel (GGA)2 motifs in vivo, we reasoned that occasional TGCAA pentamers interspersed among (TG-GAA), repeats might promote folding back of the chain on itself by forming GCA-turn loops, and thus modulate centromere folding. In the present paper, we have used NMR, distance geometry, restrained molecular dynamics, and backcalculation refinement to study the solution structure of the DNA heptadecamer (G)TGGAATGCAATGGAA(C), which contains three centromeric pentamer repeats, the middle one of which is changed from TG...

show abstract

Section: Structural Featuressupporting

confidence: 57%

supporting

confidence: 60%

Section: Spectral Analysismentioning

confidence: 97%

mentioning

confidence: 99%

See 2 more Smart Citations

A single G-to-C change causes human centromere TGGAA repeats to fold back into hairpins.

Zhu

Chou

Reid

1996

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The arrowheads indicate the major primer extension product and the corresponding site of transcription initiation at the mutant promoter. the loop-closing base pair (G-14, C-10) are essential for the formation of an unusually stable template-strand hairpin (Hirao et al 1994;Chou et al 1996;Dai et al 1997). This hairpin drives extrusion from supercoiled, double-stranded DNA (Dai et al 1998).…”

Section: Role Of Promoter Sequences In the Supercoil-driven Formationmentioning

confidence: 99%

Sequence and DNA structural determinants of N4 virion RNA polymerase–promoter recognition

Dai¹,

Rothman-Denes²

1998

Genes Dev.

View full text Add to dashboard Cite

Coliphage N4-coded, virion-encapsidated RNA polymerase (vRNAP) is able to bind to and transcribe promoter-containing double-stranded DNAs when the template is supercoiled and Escherichia coli single-stranded DNA-binding protein (Eco SSB) is present. We report that vRNAP-promoter recognition and activity on these templates require specific sequences and a hairpin structure on the template strand. Hairpin extrusion, induced by Mg(II) and physiological superhelical density, is essential to provide the correct DNA structure for polymerase recognition, as mutant promoters that do not form hairpins show reduced in vitro activity. Therefore, a supercoil-induced DNA structural transition regulates N4 vRNAP transcription. Eco SSB activates transcription at physiological superhelical densities by stabilizing the template-strand hairpin. Specific sequences at the promoters are conserved to provide proper contacts for vRNAP, to support hairpin extrusion, or both. We propose a model for in vivo utilization of the vRNAP promoters, and discuss the roles of DNA supercoiling and Eco SSB in promoter activation.

show abstract

Hexamer oligonucleotide topology and assembly under solution phase NMR and theoretical modeling scrutiny

et al. 2010

View full text Add to dashboard Cite

The entire family of noncomplementary hexamer oligodeoxyribonucleotides d(GCXYGC) (X and Y = A, G, C, or T) were assessed for topological indicators and equilibrium thermodynamics using a priori molecular modeling and solution phase NMR spectroscopy. Feasible modeled hairpin structures formed a basis from which solution structure and equilibria for each oligonucleotide were considered. ¹H and ³¹P variable temperature-dependent (VT) and concentration-dependent NMR data, NMR signal assignments, and diffusion parameters led to d(GCGAGC) and d(GCGGGC) being understood as exceptions within the family in terms of self-association and topological character. A mean diffusion coefficient D(298 K) = (2.0 ± 0.07) × 10⁻¹⁰ m² s⁻¹ was evaluated across all hexamers except for d(GCGAGC) (D(298 K) = 1.7 × 10⁻¹⁰ m² s⁻¹) and d(GCGGGC) (D(298 K) = 1.2 × 10⁻¹⁰ m² s⁻¹). Melting under VT analysis (T(m) = 323 K) combined with supporting NMR evidence confirmed d(GCGAGC) as the shortest tandem sheared GA mismatched duplex. Diffusion measurements were used to conclude that d(GCGGGC) preferentially exists as the shortest stable quadruplex structure. Thermodynamic analysis of all data led to the assertion that, with the exception of XY = GA and GG, the remaining noncomplementary oligonucleotides adopt equilibria between monomer and duplex, contributed largely by monomer random-coil forms. Contrastingly, d(GCGAGC) showed preference for tandem sheared GA mismatch duplex formation with an association constant K = 3.9 × 10⁵M⁻¹. No direct evidence was acquired for hairpin formation in any instance although its potential existence is considered possible for d(GCGAGC) on the basis of molecular modeling studies.

show abstract

On the Relative Ability of Centromeric GNA Triplets to Form HairpinsversusSelf-paired Duplexes

Cited by 36 publications

References 16 publications

A single G-to-C change causes human centromere TGGAA repeats to fold back into hairpins.

A single G-to-C change causes human centromere TGGAA repeats to fold back into hairpins.

Sequence and DNA structural determinants of N4 virion RNA polymerase–promoter recognition

Hexamer oligonucleotide topology and assembly under solution phase NMR and theoretical modeling scrutiny

Contact Info

Product

Resources

About