Influence of loop residues on the relative stabilities of DNA hairpin structures.

Senior, Mary M.; Jones, R. A. C.; Breslauer, Kenneth J.

doi:10.1073/pnas.85.17.6242

Cited by 155 publications

(117 citation statements)

References 41 publications

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“…It is expected, however, that hairpins with only 3 base pairs in the stem will melt in a two-state manner. Favorable AH"'s of loop closure have also been observed for RNA and DNA hairpins with other lengths (21,22,26), although examples of unfavorable AH0's have also been reported (8,26).…”

Section: Resultsmentioning

confidence: 97%

“…Improved methods for the synthesis of RNA molecules of defined sequence allow testing the validity of these assumptions (9)(10)(11)(12)(13) Comparison of loops with first mismatches of AA and GA (Table I) suggests this model is also oversimplified. Studies of RNA and DNA hairpin loops with 4 nucleotides also reveal a significant sequence dependence (22,(24)(25)(26). Early models of loop initiation suggested that loops closed by GC pairs are 2 kcal/mol more stable than loops closed by AU pairs (6).…”

Section: Resultsmentioning

confidence: 99%

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RNA hairpin loop stability depends on closing base pair

Serra¹,

Lyttle²,

Axenson³

et al. 1993

Nucl Acids Res

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

RNA hairpin loop stability depends on closing base pair

Serra¹,

Lyttle²,

Axenson³

et al. 1993

Nucl Acids Res

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“…To isolate the thermodynamic contribution of order in the triplet repeat loop regions of these hairpins, we have compared these hairpins to the similarly constructed hairpin, X[TTT] 6 X. Implicit in the choice of X[TTT] 6 X as a thermodynamic reference is the assumption that the all-T loop resembles, more than any other base combination, an unstructured loop (47,(49)(50)(51)(52)(53)(54). In support of this assumption, we note that the measured enthalpy for X[TTT] 6 X is in good agreement with the enthalpy predicted by nearest-neighbor data (55,56) for the hairpin stem.…”

Section: Resultsmentioning

confidence: 99%

Conformational energetics of stable and metastable states formed by DNA triplet repeat oligonucleotides: Implications for triplet expansion diseases

Völker

Makube

Plum

et al. 2002

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

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We have embedded the hexameric triplet repeats (CAG)6 and (CTG) 6 between two (GC)3 domains to produce two 30-mer hairpins with the sequences d[(GC) 3(CAG)6(GC)3] and d[(GC)3(CTG)6(GC)3]. This construct reduces the conformational space available to these repetitive DNA sequences. We find that the (CAG) 6 and (CTG)6 repeats form stable, ordered, single-stranded structures. These structures are stabilized at 62°C by an average enthalpy per base of 1.38 kcal⅐mol ؊1 for the CAG triplet and 2.87 kcal⅐mol ؊1 for the CTG triplet, while being entropically destabilized by 3.50 cal⅐K ؊1 ⅐mol ؊1 for the CAG triplet and 7.6 cal⅐K ؊1 ⅐mol ؊1 for the CTG triplet. Remarkably, these values correspond, respectively, to 1͞3 (for CAG) and 2͞3 (for CTG) of the enthalpy and entropy per base values associated with Watson-Crick base pairs. We show that the presence of the loop structure kinetically inhibits duplex formation from the two complementary 30-mer hairpins, even though the duplex is the thermodynamically more stable state. Duplex formation, however, does occur at elevated temperatures. We propose that this thermally induced formation of a more stable duplex results from thermal disruption of the single-stranded order, thereby allowing the complementary domains to associate (perhaps via "kissing hairpins"). Our melting profiles show that, once duplex formation has occurred, the hairpin intermediate state cannot be reformed, consistent with our interpretation of kinetically trapped hairpin structures. The duplex formed by the two complementary oligonucleotides does not have any unusual optical or thermodynamic properties. By contrast, the very stable structures formed by the individual single-stranded triplet repeat sequences are thermally and thermodynamically unusual. We discuss this stable, triplet repeat, single-stranded structure and its interconversion with duplex in terms of triplet expansion diseases.

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“…Most of the previous studies of hairpins deal with the structure of the folded state or with the thermodynamics of the folding-unfolding transitions (5)(6)(7). Knowledge about the kinetics of the hairpin transitions is limited to a few isolated measurements of the characteristic rates (8,9).…”

mentioning

confidence: 99%

Kinetics of conformational fluctuations in DNA hairpin-loops

Bonnet

Krichevsky

Libchaber

1998

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

528

560

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The kinetics of DNA hairpin-loop f luctuations has been investigated by using a combination of f luorescence energy transfer and f luorescence correlation spectroscopy. We measure the chemical rates and the activation energies associated with the opening and the closing of the hairpin for different sizes and sequences of the loop and for various salt concentrations. The rate of unzipping of the hairpin stem is essentially independent of the characteristics of the loop, whereas the rate of closing varies greatly with the loop length and sequence. The closing rate scales with the loop length, with an exponent 2.6 ؎ 0.3. The closing rate is increased at higher salt concentrations. For hairpin closing, a loop of adenosine repeats leads to smaller rates and higher activation energies than a loop with thymine repeats.DNA hairpin structures may participate in many biological functions, such as the regulation of gene expression (1), DNA recombination (2), and facilitation of mutagenic events (3). Hairpin-loops were proposed as antisense drugs with high resistance to degradation by exonucleases (4).Hairpin structures are not static: they fluctuate between different conformations. In a simplified description, all of the conformations can be divided into two main states: the open state and the closed one (Fig. 1). The closed state is characterized by a low enthalpy due to base pairing in the stem region of the hairpin. The open state has a high entropy due to the large number of configurations achievable by a single-stranded DNA chain. The closed-to-open transition requires an energy fluctuation sufficiently large to unzip all of the base pairs, whereas the opposite (closing) transition involves the collision of the two arms of a hairpin, followed by the nucleation and the propagation of a base-paired stretch. One expects the rate of closing to depend strongly on the properties of the hairpin loop, such as length and rigidity, whereas one expects the rate of opening to be relatively unaffected by these properties.Most of the previous studies of hairpins deal with the structure of the folded state or with the thermodynamics of the folding-unfolding transitions (5-7). Knowledge about the kinetics of the hairpin transitions is limited to a few isolated measurements of the characteristic rates (8, 9). The dependence of closing and opening rates on such crucial parameters as the loop size, the loop sequence, and the salt concentration have not been reported, and the activation energies of the transitions are not known.We present here measurements of the characteristic rates of closing and of opening for different lengths and sequences of the loop, done in a wide range of temperatures and salt concentrations. We find that the characteristics of the loop influence the closing rate much more strongly than the opening rate. The rate of closing decreases when the loop size increases. This dependence can be approximated by a scaling relationship with an exponent of 2.6 Ϯ 0.3. The change of poly(T) sequence in the loop to poly...

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Influence of loop residues on the relative stabilities of DNA hairpin structures.

Cited by 155 publications

References 41 publications

RNA hairpin loop stability depends on closing base pair

RNA hairpin loop stability depends on closing base pair

Conformational energetics of stable and metastable states formed by DNA triplet repeat oligonucleotides: Implications for triplet expansion diseases

Kinetics of conformational fluctuations in DNA hairpin-loops

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