Thermodynamics of the B to Z transition in poly(m5dG-dC).

Chaires, Jonathan B.; Sturtevant, Julian M.

doi:10.1073/pnas.83.15.5479

Cited by 43 publications

(31 citation statements)

References 24 publications

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“…Differential Scanning Calorimetry, with significant advantage over the method based on indirect Van't Hoff analysis , provides a direct, model‐independent determination of the order─disorder denaturation transition in oligonucleotides or their secondary structures such as G‐quadruplexes. The calorimetric transition curves are shown in Figure .…”

Section: Resultsmentioning

confidence: 99%

Expression of Concern: The Truncated Human Telomeric Sequence forms a Hybrid‐Type Intramolecular Mixed Parallel/antiparallel G‐quadruplex Structure in K⁺ Solution

2016

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In 80-90% tumor cells, telomerase becomes active and stabilizes the length of telomeres. The formation and stabilization of G-quadruplexes formed from human telomeric sequences have been proved able to inhibit the activity of telomerase, thus human telomeric G-quadruplex structure has become a potential target for the development of cancer therapy. Hence, structure of G-quadruplex formed in K(+) solution has been an attractive hotspot for further studies. However, the exact structure of human telomeric G-quadruplex in K(+) is extremely controversial, this study provides information for the understanding of different G-quadruplexes. Here, we report that 22nt and 24nt human telomeric sequences form unimolecular hybrid-type mixed parallel/antiparallel G-quadruplex in K(+) solution elucidated utilizing Circular Dichroism, Differential Scanning Calorimetry, and gel electrophoresis. Moreover, individual configuration of these two sequences was speculated in this study. The detailed structure information of the G-quadruplex formed under physiologically relevant condition is necessary for structure-based rational drug design.

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Section: Resultsmentioning

confidence: 99%

Expression of Concern: The Truncated Human Telomeric Sequence forms a Hybrid‐Type Intramolecular Mixed Parallel/antiparallel G‐quadruplex Structure in K⁺ Solution

2016

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“…Values and temperature dependence of the heat capacity change DC p o are directly obtained by means of differential scanning calorimetry (DSC) (Krupakar et al, 1999;Rosgen & Hinz, 2002). Differences between calorimetric (DH cal o ) and van't Hoff (DH vH o ) enthalpy is a well-known phenomenon in the case of departure from the all-or-none (cooperative) model in a phase transition of macromolecules, like protein folding/unfolding or the helix-to-coil transition of nucleic acids (see, e.g., Chaires & Sturtevant, 1986;Wu & Sugimoto, 2000). For intermolecular association the observed differences in the enthalpy estimates have given rise to numerous empirical and theoretical analyses.…”

Section: Methodology Of the Thermodynamic Approachmentioning

confidence: 99%

Thermodynamics of specific protein-RNA interactions.

Stolarski¹

2003

Acta Biochim Pol

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Description of the recognition specificity between proteins and nucleic acids at the level of molecular interactions is one of the most challenging tasks in biophysics. It is key to understanding the course and control of gene expression and to the application of the thus acquired knowledge in chemotherapy. This review presents experimental results of thermodynamic studies and a discussion of the role of thermodynamics in formation and stability of functional protein-RNA complexes, with a special attention to the interactions involving mRNA 5' cap and cap-binding proteins in the initiation of protein biosynthesis in the eukaryotic cell. A theoretical framework for analysis of the thermodynamic parameters of protein-nucleic acid association is also briefly surveyed. Overshadowed by more spectacular achievements in structural studies, the thermodynamic investigations are of equal importance for full comprehension of biopolymers' activity in a quantitative way. In this regard, thermodynamics gives a direct insight into the energetic and entropic characteristics of complex macromolecular systems in their natural environment, aqueous solution, and thus complements the structural view derived from X-ray crystallography and multidimensional NMR. Further development of the thermodynamic approach toward interpretation of recognition and binding specificity in terms of molecular biophysics requires more profound contribution from statistical mechanics.

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“…The hypomethylation of gene regulatory regions is often connected to an expressed state of those genes, whereas silent genes are generally overmethylated. In vitro, cytosine methylation also facilitates the B-to-Z transition in synthetic linear DNA polymers (1,2,5) and in certain sequences in supercoiled recombinant plasmids (10,25).…”

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confidence: 99%

Cytosine methylation enhances Z-DNA formation in vivo

1990

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The influence of cytosine methylation on the supercoil-stabilized B-Z equilibrium in Escherichia coli was analyzed by two independent assays. Both the M EcoRI inhibition assay and the linking-number assay have been used previously to establish that dC-dG segments of sufficient lengths can exist as left-handed helices in vivo. A series of dC-dG plasmid inserts with Z-form potential, ranging in length from 14 to 74 base pairs, was investigated. Complete methylation of cytosine at all HhaI sites, including the inserts, was obtained by coexpression of the HhaI methyltransferase (M -HhaI) in cells also carrying a dC-dG-containing plasmid. Both assays showed that for all lengths of dC-dG inserts, the relative amounts of B and Z helices were shifted to more Z-DNA in the presence of M -HhaI than in the absence of M HhaI. These results indicate that cytosine methylation enhances the formation of Z-DNA helices at the superhelix density present in E. coli. The B-Z equilibrium, in combination with site-specific base methylation, may constitute a concerted mechanism for the modulation of DNA topology and DNA-protein interactions.DNA structural microheterogeneity is believed to play a fundamental role in genetic regulatory mechanisms (16,20). Left-handed DNA (Z-DNA) is a structural alternative to right-handed DNA (B-DNA) that has been well characterized in vitro (14,17,21). Recently, it was demonstrated that Z-DNA can exist in living Escherichia coli cells and that a given sequence can coexist in the Z form and the B form in the same cell (7,8,15,22,23). The in vivo B-Z equilibrium is influenced by active biological processes (like transcription, replication, supercoil and toroid formations, and DNAprotein interactions).There is evidence that cytosine methylation may have an important signaling function in eucaryotic gene expression (4, 11). The hypomethylation of gene regulatory regions is often connected to an expressed state of those genes, whereas silent genes are generally overmethylated. In vitro, cytosine methylation also facilitates the B-to-Z transition in synthetic linear DNA polymers (1, 2, 5) and in certain sequences in supercoiled recombinant plasmids (10,25).In previous studies, we employed two independent assays for structural analyses under in vivo conditions. The first assay was based on the observation that a recognition sequence (GAATTC) is not methylated by the corresponding bacterial methyltransferase (M EcoRI) when this site is near or inside a left-handed helix, whereas other EcoRI sites in the same plasmid molecule were completely methylated (8,23). The presence of a Z structure around the unmethylated sites was confirmed by a variety of chemical, enzymatic, and topological approaches (14,16,17,21,24 On this basis, the formation of Z-DNA inside growing bacterial cells could be analyzed by a linking-number assay. The B-to-Z transition inside E. coli cells results in the relaxation of a number of supercoils, in proportion to the length of the Z-region involved. This process causes DNA gyrase to decrease...

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Thermodynamics of the B to Z transition in poly(m5dG-dC).

Cited by 43 publications

References 24 publications

Expression of Concern: The Truncated Human Telomeric Sequence forms a Hybrid‐Type Intramolecular Mixed Parallel/antiparallel G‐quadruplex Structure in K⁺ Solution

Expression of Concern: The Truncated Human Telomeric Sequence forms a Hybrid‐Type Intramolecular Mixed Parallel/antiparallel G‐quadruplex Structure in K⁺ Solution

Thermodynamics of specific protein-RNA interactions.

Cytosine methylation enhances Z-DNA formation in vivo

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Thermodynamics of the B to Z transition in poly(m5dG-dC).

Cited by 43 publications

References 24 publications

Expression of Concern: The Truncated Human Telomeric Sequence forms a Hybrid‐Type Intramolecular Mixed Parallel/antiparallel G‐quadruplex Structure in K+ Solution

Expression of Concern: The Truncated Human Telomeric Sequence forms a Hybrid‐Type Intramolecular Mixed Parallel/antiparallel G‐quadruplex Structure in K+ Solution

Thermodynamics of specific protein-RNA interactions.

Cytosine methylation enhances Z-DNA formation in vivo

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Expression of Concern: The Truncated Human Telomeric Sequence forms a Hybrid‐Type Intramolecular Mixed Parallel/antiparallel G‐quadruplex Structure in K⁺ Solution

Expression of Concern: The Truncated Human Telomeric Sequence forms a Hybrid‐Type Intramolecular Mixed Parallel/antiparallel G‐quadruplex Structure in K⁺ Solution