Thermodynamics of an Intramolecular DNA Triple Helix: A Calorimetric and Spectroscopic Study of the pH and Salt Dependence of Thermally Induced Structural Transitions

Ge, Plum; Kj, Breslauer

doi:10.1006/jmbi.1995.0251

Cited by 118 publications

(145 citation statements)

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“…The tendency for protonation of the N3 atom of dCTP has been discussed in several other pol ⅐DNA structures with both native and adducted purines in the templates (8,15,16). Although the N3 atom of free cytosine has a pK a ϳ4.5, the local molecular environment could elevate the pK a to 6.2-7.2 at a terminal position or Ͼ8.5 at an internal position in DNA triple helices (52,53). Nair et al (8) suggested that an elevation of the pK a of dCTP could be due to the basestacking and long range electrostatic interactions of the active site residues Asp-126 and Glu-127.…”

Section: Table 2 Summary Of Pol Extension Products From Lc-ms/ms Analmentioning

confidence: 99%

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases

Zhao

Pence

Christov

et al. 2012

Journal of Biological Chemistry

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N2,3-Ethenoguanine (N2,3-ϵG) is one of the exocyclic DNA adducts produced by endogenous processes (e.g. lipid peroxidation) and exposure to bioactivated vinyl monomers such as vinyl chloride, which is a known human carcinogen. Existing studies exploring the miscoding potential of this lesion are quite indirect because of the lability of the glycosidic bond. We utilized a 2′-fluoro isostere approach to stabilize this lesion and synthesized oligonucleotides containing 2′-fluoro-N2,3-ϵ-2′-deoxyarabinoguanosine to investigate the miscoding potential of N2,3-ϵG by Y-family human DNA polymerases (pols). In primer extension assays, pol η and pol κ replicated through N2,3-ϵG, whereas pol ι and REV1 yielded only 1-base incorporation. Steady-state kinetics revealed that dCTP incorporation is preferred opposite N2,3-ϵG with relative efficiencies in the order of pol κ > REV1 > pol η ≈ pol ι, and dTTP misincorporation is the major miscoding event by all four Y-family human DNA pols. Pol ι had the highest dTTP misincorporation frequency (0.71) followed by pol η (0.63). REV1 misincorporated dTTP and dGTP with much lower frequencies. Crystal structures of pol ι with N2,3-ϵG paired to dCTP and dTTP revealed Hoogsteen-like base pairing mechanisms. Two hydrogen bonds were observed in the N2,3-ϵG:dCTP base pair, whereas only one appears to be present in the case of the N2,3-ϵG:dTTP pair. Base pairing mechanisms derived from the crystal structures explain the slightly favored dCTP insertion for pol ι in steady-state kinetic analysis. Taken together, these results provide a basis for the mutagenic potential of N2,3-ϵG.

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Section: Table 2 Summary Of Pol Extension Products From Lc-ms/ms Analmentioning

confidence: 99%

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases

Zhao

Pence

Christov

et al. 2012

Journal of Biological Chemistry

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“…This sequence has several GG base steps and it is suggested that this dinucleotide has a tendency towards bistability that can be explained by steric and electrostatic interactions. 33 A similar melting transition has been reported for an intramolecular DNA triple helix 34 in a 31-mer oligonucleotide. This sequence can thus be further studied under conditions favoring biphasic transitions to determine the intermediate structure.…”

Section: Discussionmentioning

confidence: 55%

Structural properties of DNA oligomers containing (GACX)_n and (GAXC)_n tandem repeats

2011

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The antisense DNA sequence of mature mouse micro RNA, miR341, includes three repeats of the tetranucleotide (GACC). The -GAC- repeat is known to form a parallel duplex, in acidic environments. The thermal melting profile of miR341 DNA, at pH 4, 5, and 6 indicates the formation of a very stable structure, which loses its stability when pH is increased. Thus, the addition of a cytosine at the 3' end of the (GAC) motif preserves the molecule's potential to fold into an unusual structure at low pH. The effect of modifying the nucleotide composition of the GACC sequence on the secondary structures formed by oligomers containing seven tandem repeats of the altered motifs was examined here. UV melting profiles were determined, as a function of pH, for 28-mers of the two series (GAXC)(7) and (GACX)(7) (X= A/C/T/G)(.) The sequence (GACC)(7) was found to be extremely sensitive to pH variations, with a stable structure formed at pH 5 (T(m) ≥ 60°C). NMR spectroscopy established that the low pH structure is not B-DNA. (GACA)(7) and (GACT)(7) also formed stable structures at low pH but the addition of guanine at the 3'end, as seen in the (GACG) series resulted in the loss of this property. Introducing a break in the 5'-GAC-3' motif, explored in the (GAXC) series, also inhibits formation of stable structures under acidic conditions.

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“…The maximum formal value is 2.5 protons per monomer (10 protons per tetraplex). The observation that net proton release is less than the theoretical number of protons assumed to be associated with the d(TC 5 ) structure (less than complete protonation of potential sites) is, as one would expect, because of end effects and͞or negative cooperativity between adjacent cytosines, influences that have been reported for DNA triplexes (33)(34)(35)(36)(37). The point is that the sensitivity of the T m of poly(A) to solution conditions makes it a sensitive probe for characterizing solution pH.…”

Section: Poly(a) As a Molecular Probe Of Ph And Protonsmentioning

confidence: 93%

Communication between noncontacting macromolecules

Völker

Klump

Breslauer³

2001

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

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We present a quantitative experimental demonstration of solventmediated communication between noncontacting biopolymers. We show that changes in the activity of a solvent component brought about by a conformational change in one biopolymer can result in changes in the physical properties of a second noncontacting biopolymer present in solution. Specifically, we show that the release of protons on denaturation of a donor polymer (in this case, a four-stranded DNA tetraplex, iDNA) modulates the melting temperature of a noncontacting, acceptor polymer [in this case poly(A)]. In addition to such proton-mediated cross talk, we also demonstrate counterion-mediated cross talk between noncontacting biopolymers. Specifically, we show that counterion association͞release on denaturation of native salmon sperm DNA (the donor polymer) can modulate the melting temperature of poly(dA)⅐poly(dT) (the acceptor polymer). Taken together, these two examples demonstrate how poly(A) and poly(dA)⅐poly(dT) can serve as molecular probes that report the pH and free salt concentrations in solution, respectively. Further, we demonstrate how such through-solvent dialogue between biopolymers that do not directly interact can be used to evaluate (in a model-free manner) association͞dissociation reactions of solvent components (e.g., protons, sodium cations) with one of the two biopolymers. We propose that such through-solution dialogue is a general property of all biopolymers. As a result, such solvent-mediated cross talk should be considered when assessing reactions of multicomponent systems such as those that exist in essentially all biological processes.

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Thermodynamics of an Intramolecular DNA Triple Helix: A Calorimetric and Spectroscopic Study of the pH and Salt Dependence of Thermally Induced Structural Transitions

Cited by 118 publications

References 0 publications

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases

Structural properties of DNA oligomers containing (GACX)_n and (GAXC)_n tandem repeats

Communication between noncontacting macromolecules

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Thermodynamics of an Intramolecular DNA Triple Helix: A Calorimetric and Spectroscopic Study of the pH and Salt Dependence of Thermally Induced Structural Transitions

Cited by 118 publications

References 0 publications

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases

Structural properties of DNA oligomers containing (GACX)n and (GAXC)n tandem repeats

Communication between noncontacting macromolecules

Contact Info

Product

Resources

About

Structural properties of DNA oligomers containing (GACX)_n and (GAXC)_n tandem repeats