Divalent Cations Stabilize Unstacked Conformations of DNA and RNA by Interacting with Base Π Systems

McFail-Isom, Lori; Shui, Xiuqi; Williams, Loren Dean

doi:10.1021/bi982201+

Cited by 133 publications

(123 citation statements)

References 26 publications

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“…We also found that the existence of magnesium could significantly favor the nonhysteretic transition of endclosed DNA (Fig. 5), which is similar to our previous results that the existence of magnesium could favor the nonhysteretic transition on end-opened λ-DNA (10), likely due to the enhancement of the DNA base-pair stability by magnesium (25).…”

Section: Discussionsupporting

confidence: 91%

Revealing the competition between peeled ssDNA, melting bubbles, and S-DNA during DNA overstretching by single-molecule calorimetry

Zhang

Chen

et al. 2013

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

131

165

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Double-stranded DNA (dsDNA) unconstrained by torsion undergoes an overstretching transition at about 65 pN, elongating the DNA to about 1.7-fold. Three possible structural transitions have been debated for the nature of DNA overstretching: (i) "peeling" apart of dsDNA to produce a peeled ssDNA strand under tension while the other strand coils, (ii) "inside-strand separation" of dsDNA to two parallel ssDNA strands that share tension (melting bubbles), and (iii) "B-to-S" transition to a novel dsDNA, termed S-DNA. Here we overstretched an end-opened DNA (with one open end to allow peeling) and an end-closed (i.e., both ends of the linear DNA are covalently closed to prohibit peeling) and torsion-unconstrained DNA. We report that all three structural transitions exist depending on experimental conditions. For the end-opened DNA, the peeling transition and the B-to-S transition were observed; for the end-closed DNA, the inside-strand separation and the B-to-S transition were observed. The peeling transition and the inside-strand separation are hysteretic and have an entropy change of approximately 17 cal/(K·mol), whereas the B-to-S transition is nonhysteretic and has an entropy change of approximately −2 cal/(K·mol). The force-extension curves of peeled ssDNA, melting bubbles, and S-DNA were characterized by experiments. Our results provide experimental evidence for the formation of DNA melting bubbles driven by high tension and prove the existence of nonmelted S-DNA. Our findings afford a full understanding of three possible force-driven structural transitions of torsion-unconstrained DNA and the resulting three overstretched DNA structures.DNA bubble | magnetic tweezers

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Section: Discussionsupporting

confidence: 91%

Revealing the competition between peeled ssDNA, melting bubbles, and S-DNA during DNA overstretching by single-molecule calorimetry

Zhang

Chen

et al. 2013

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

131

165

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“…These results suggest that zinc could have an unstacking function in the adenine DNA glycosylase activity of gelonin. This would support the proposal by McFail-Isom et al (48) that cations have mechanistic roles in DNA bending, strand separation, DNA-protein recognition, base flipping, RNA folding, and catalysis through -interactions with the faces of DNA and RNA bases.…”

Section: Discussionsupporting

confidence: 88%

Gelonin Is an Unusual DNA Glycosylase That Removes Adenine from Single-stranded DNA, Normal Base Pairs and Mismatches

Nicolas

Beggs

Taraschi

2000

Journal of Biological Chemistry

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We reported that plant ribosome inactivating proteins (RIP) have a unique DNA glycosylase activity that removes adenine from single-stranded DNA (Nicolas, E., Beggs, J. M., Haltiwanger, B. M., and Taraschi, T. F. (1998) J. Biol. Chem. 273, 17216 -17220). In this investigation, we further characterized the interaction of the RIP gelonin with single-stranded oligonucleotides and investigated its activity on double-stranded oligonucleotides. At physiological pH, zinc and ␤-mercaptoethanol stimulated the adenine DNA glycosylase activity of gelonin. Under these conditions, gelonin catalytically removed adenine from single-stranded DNA and, albeit to a lesser extent, from normal base pairs and mismatches in duplex DNA. Also unprecedented was the finding that activity on single-stranded and double-stranded oligonucleotides containing multiple adenines generated unstable products with several abasic sites, producing strand breakage and duplex melting, respectively. The results from competition experiments suggested similar interactions between gelonin's DNA-binding domain and oligonucleotides with and without adenine. A reexamination of the classification of gelonin as a DNA glycosylase/AP lyase using the borohydride trapping assay revealed that gelonin was similar to the DNA glycosylase MutY: both enzymes are monofunctional glycosylases, which are trappable to their DNA substrates. The k cat for the removal of adenine from single-stranded DNA was close to the values observed with multisubstrate DNA glycosylases, suggesting that the activity of RIPs on DNA may be physiologically relevant.

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“…Williams and coworkers (32) reported a crystal structure of the d(CGCGAATTCGCG) duplex at 1.4 Å that was interpreted in terms of fractional occupancy of ions in the grooves of DNA. Subsequently, the ions Rb ϩ and Tl ϩ have been reported crystallographically in the spine of hydration at the ATT region (1,33,34), and Rb ϩ was located in the minor groove (35,36). The issue was revisited by Dickerson et al (37) in a high-resolution crystal structure determination that argued against ions in the minor groove, and the Williams group responded (38).…”

Section: Introductionmentioning

confidence: 99%

Ion motions in molecular dynamics simulations on DNA

Ponomarev

Thayer

Beveridge

2004

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

224

246

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Counterions play a significant role in DNA structure and function, and molecular dynamics (MD) simulations offer the prospect of detailed description of the dynamical structure of ions at the molecular level. However, the motions of mobile counterions are notably slow to converge in MD on DNA. Obtaining accurate and reliable MD simulations requires knowing just how much sampling is required for convergence of each of the properties of interest. To address this issue, MD on a d(CGCGAATTCGCG) duplex in a dilute aqueous solution of water and 22 Na ؉ counterions was performed until convergence was achieved. The calculated first shell ion occupancies and DNA-Na ؉ radial distribution functions were computed as a function of time to assess convergence, and compared with relaxation times of the DNA internal parameters shift, slide, rise, tilt, roll, and twist. The sequence dependence of fractional occupancies of ions in the major and minor grooves of the DNA is examined, and the possibility of correlation between ion proximity and DNA minor groove widths is investigated. C ounterion structures and motions have been implicated in recent ideas about sequence effects on DNA structure axis curvature and ligand-induced bending (1-7). In each of these theories, the local interactions of ions with polyionic DNA complement the effects described by counterion condensation (CC) theory (8) and the Poisson Boltzmann (PB) equation (9,10). Although the effect of ions and ionic strength on DNA structural and thermodynamics properties are implied from diverse experiments, obtaining a fully detailed molecular model of the ions interacting with DNA based on these results is usually not possible. Oligonucleotide crystal structures reveal only the few ions that are ordered and can be unequivocally assigned. The positions of ions around DNA are generally underdetermined in experiments based on biophysical methods. Recent studies requiring this information have turned to large-scale molecular dynamics (MD) simulations to obtain computational models (11). However, in MD modeling, the complex aggregate of oligonucleotide, water, counterions, and coions is slow to fully stabilize, and ion motions are a rate-determining step in total convergence (12). Current reviews of MD on DNA (12)(13)(14) indicate that all simulations to date are based on considerably shorter trajectories. Therefore, we initiated a project aimed at obtaining demonstrably converged results on ion structures and motions. A related question is the sensitivity of the fast internal motions of the DNA to ion convergence. Our analysis is based on an MD simulation on the prototype B-form duplex d(CGC-GAATTCGCG) in a dilute aqueous solution of water and Na ϩ counterions carried out on a supercomputer until the point of convergence could be reliably determined. The trajectories are used to study the sequence dependence of ion distributions, the DNA-Na ϩ radial distribution functions, and the sensitivity of groove widths to ion proximity. The simulations are used as a basis for a compa...

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Divalent Cations Stabilize Unstacked Conformations of DNA and RNA by Interacting with Base Π Systems

Cited by 133 publications

References 26 publications

Revealing the competition between peeled ssDNA, melting bubbles, and S-DNA during DNA overstretching by single-molecule calorimetry

Revealing the competition between peeled ssDNA, melting bubbles, and S-DNA during DNA overstretching by single-molecule calorimetry

Gelonin Is an Unusual DNA Glycosylase That Removes Adenine from Single-stranded DNA, Normal Base Pairs and Mismatches

Ion motions in molecular dynamics simulations on DNA

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