Nucleic Acid Helix Stability: Effects of Salt Concentration, Cation Valence and Size, and Chain Length

Tan, Zhi-Jie; Chen, Shi‐Jie

doi:10.1529/biophysj.105.070904

Cited by 301 publications

(421 citation statements)

References 104 publications

(216 reference statements)

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“…A heterogeneous (sequence specific) salt correction could provide consistent results with the experiment. Such deviations are not unexpected, given the differences in solvation between specific nucleotides and salt ions (27,28), however the effect has never been quantified in the context of polymeric DNA. With this goal in mind, we applied our fitting algorithm to extract NNBP energies for data taken at many salt concentrations (Fig.…”

Section: Resultsmentioning

confidence: 99%

Single-molecule derivation of salt dependent base-pair free energies in DNA

Huguet

Bizarro

Forns

et al. 2010

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

232

298

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Accurate knowledge of the thermodynamic properties of nucleic acids is crucial to predicting their structure and stability. To date most measurements of base-pair free energies in DNA are obtained in thermal denaturation experiments, which depend on several assumptions. Here we report measurements of the DNA base-pair free energies based on a simplified system, the mechanical unzipping of single DNA molecules. By combining experimental data with a physical model and an optimization algorithm for analysis, we measure the 10 unique nearest-neighbor base-pair free energies with 0.1 kcal mol −1 precision over two orders of magnitude of monovalent salt concentration. We find an improved set of standard energy values compared with Unified Oligonucleotide energies and a unique set of 10 base-pair-specific salt-correction values. The latter are found to be strongest for AA/TT and weakest for CC/GG. Our unique energy values and salt corrections improve predictions of DNA unzipping forces and are fully compatible with melting temperatures for oligos. The method should make it possible to obtain free energies, enthalpies, and entropies in conditions not accessible by bulk methodologies.DNA thermodynamics | DNA unzipping | nearest-neighbor model | optical tweezers T he nearest-neighbor (NN) model (1-4) for DNA thermodynamics has been successfully applied to predict the free energy of formation of secondary structures in nucleic acids. The model estimates the free-energy change to form a double helix from independent strands as a sum over all of resulting bp and adjacent-bp stacks, depending on the constituent four bases of the stack, by using 10 nearest-neighbor base-pair (NNBP) energies. These energies themselves contain contributions from stacking, hydrogen-bonding, and electrostatic interactions as well as configurational entropy loss. Accurately predicting free energies has many applications in biological science: to predict self-assembled structures in DNA origami (5, 6); achievement of high selectivity in the hybridization of synthetic DNAs (7); antigene targeting and siRNA design (8); characterization of translocating motion of enzymes that mechanically disrupt nucleic acids (9); prediction of nonnative states (e.g., RNA misfolding) (10); and DNA guided crystallization of colloids (11).Some of the most reliable estimates of the NNBP energies to date have been obtained from thermal denaturation studies of DNA oligos and polymers (2). Although early studies showed large discrepancies in the NNBP values, nowadays they are remarkably consistent among several groups. In these studies it is assumed that duplexes melt in a two-state fashion. However this assumption is not often the case and a discrepancy between the values obtained using oligomers vs. polymers remains a persistent problem that has been attributed to many factors such as the slow dissociation kinetics induced by a population of transient nondenatured intermediates that develop during thermal denaturation experiments (12). Single-molecule techniques (13) circ...

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Section: Resultsmentioning

confidence: 99%

Single-molecule derivation of salt dependent base-pair free energies in DNA

Huguet

Bizarro

Forns

et al. 2010

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

232

298

View full text Add to dashboard Cite

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“…Simulation has suggested that PB theory is inadequate for describing electrostatic energies for nucleic acids in the presence of divalent ions such as Mg 2+ , a conclusion supported by experiments assessing the effects of ions on DNA duplex stability ( [68,69] and references therein). However, the opposite conclusion has been drawn from fitting RNA folding transitions to PB predictions [70][71][72][73][74].…”

Section: Simple Forces Underlying the Complex Behavior Of Rnamentioning

confidence: 99%

Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs

Chu

Herschlag

2008

Current Opinion in Structural Biology

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SummaryThe rapid development of our understanding of the diverse biological roles fulfilled by non-coding RNA has motivated interest in the basic macromolecular behavior, structure, and function of RNA. We focus on two areas in the behavior of complex RNAs. First, we present advances in the understanding of how RNA folding is accomplished in vivo by presenting a mechanism for the action of DEAD-box proteins. Members of this family are intimately associated with almost all cellular processes involving RNA, mediating RNA structural rearrangements and chaperoning their folding. Next, we focus on advances in understanding and characterizing the basic biophysical forces that govern the folding of complex RNAs. Ultimately we expect that a confluence and synergy between these approaches will lead to profound understanding of RNA and its biology.The explosion in our knowledge about noncoding RNA (ncRNA) -RNA that is not translated into protein -has expanded interest in RNA beyond the traditional RNA community. Diverse ncRNAs include the recently-discovered riboswitches, whose novel gene-regulation function is induced by the binding of small metabolites [1]; most of the so-called "Human Accelerated Regions" (HAR) of the human genome, whose recent evolution may be linked to the emergence of the human brain [2]; and many ncRNAs of unknown function [3]. These discoveries underscore the need to understand the fundamental macromolecular behavior of RNA, its structure and dynamics, and how these RNAs are handled and exploited in biology.Study of catalytic RNAs, which allow detection of correct folding via activity measurements, has established basic thermodynamic and kinetic properties of RNA folding. Large catalytic RNAs such as the group I intron from Tetrahymena thermophila and the RNase P RNA from Bacillus subtilis fold at vastly different rates under different conditions upon addition of Mg 2+ and have been shown to fold via multiple parallel pathways, in which different molecules follow different routes with different rates and intermediates, to a common final folded structure [4,5]. These observations support the common view that RNAs traverse rugged energy landscapes as they fold [6,7]. However, little is known about the true shape of these

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“…The nucleic acid conformation stability is related to the salt concentration and cation valence [31]. It is generally believed that the stability of DNA could be increased by enhancing the ionic strength appropriately.…”

Section: Discussionmentioning

confidence: 99%

Induced temperature-dependent DNA degradation by C60 without photoactivation

et al. 2011

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This study shows that C 60 can degrade pBR322 plasmid DNA at room temperature without photoactivation. The degradation was enhanced by increasing incubation temperature, reaction time or C 60 concentration. We also found that superoxide radical anions (O 2 · ) were formed in the C 60 solution. Superoxide dismutase significantly inhibited DNA cleavage and O 2 · generation induced by C 60 . These results suggest that DNA cleavage was caused by the formation of reactive oxygen species induced by C 60 at room temperature. Furthermore, we demonstrate that the DNA degradation was significantly inhibited by acid amide chemicals such as formamide, and by increased ionic strength of the reaction solution. These results indicate that the DNA conformation stability and the surface properties of C 60 are important factors regulating DNA degradation. We propose that C 60 can bind DNA, decrease DNA conformation stability, and induce the formation of reactive oxygen species and DNA cleavage at room temperature. Our results provide a possible explanation for the genotoxicity of C 60 , which should be considered in future use of this particular nano-material. Since the discovery of fullerene (C 60 ) in 1985, the unique physicochemical and mechanical properties of this novel carbon allotrope have attracted extensive attention, and the practical applications of fullerene as a biological and pharmacological agent have been studied [1,2]. In addition, various biological activities such as antiviral, antioxidant and chemotactic activities of fullerene derivatives have been investigated [3][4][5].In recent years, increasing numbers of publications and reports indicated that the production and use of nanoparticles may be deleterious to humans and to the environment [6][7][8]. The earlier studies showed that in several tests the acute toxicity of C 60 is low [3]. However, more recent research suggested that C 60 could induce oxidative stress in the brain of juvenile largemouth bass and the lipid peroxidation in some freshwater and marine species. Some lipid metabolism genes involved in adverse effects were found to be regulated by C 60 [9][10][11]. Furthermore, it has been shown that C 60 can impair the cell membrane by generating reactive oxygen species (ROS), and that the antibacterial activity and the genotoxicity of C 60 were also related to ROS generation [12][13][14].The results of atomistic molecular dynamics simulations and genotoxicity tests showed that C 60 could strongly bind to nucleotides and further affect the structure, stability and biological functions of DNA molecules [15,16]. It has also

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Nucleic Acid Helix Stability: Effects of Salt Concentration, Cation Valence and Size, and Chain Length

Cited by 301 publications

References 104 publications

Single-molecule derivation of salt dependent base-pair free energies in DNA

Single-molecule derivation of salt dependent base-pair free energies in DNA

Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs

Induced temperature-dependent DNA degradation by C60 without photoactivation

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