Charge Conduction Properties of a Parallel-Stranded DNA G-Quadruplex: Implications for Chromosomal Oxidative Damage

Huang, Yu Chuan; Cheng, Alan K. H.; Yu, Hua‐Zhong; Sen, Dipankar

doi:10.1021/bi9007484

Cited by 40 publications

(39 citation statements)

References 54 publications

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“…[1][2][3]. This interest is mainly due to the relevance of the charge transfer (CT) phenomenon to the oxidation damage (4,5) and to the potential application of DNA in nanoelectronics (6,7). Experimentally, charge migration through DNA can be probed either by steady-state methods based on measurements of the damage ratio (8)(9)(10) or by time-resolved spectroscopic techniques (11)(12)(13)(14).…”

mentioning

confidence: 99%

Impact of a single base pair substitution on the charge transfer rate along short DNA hairpins

Renaud

Berlin

Ratner

2013

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

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Numerical studies of hole migration along short DNA hairpins were performed with a particular emphasis on the variations of the rate and quantum yield of the charge separation process with the location of a single guanine:cytosine (G:C) base pair. Our calculations show that the hole arrival rate increases as the position of the guanine:cytosine base pair shifts from the beginning to the end of the sequence. Although these results are in agreement with recent experimental findings, the mechanism governing the charge migration along these sequences is revisited here. Instead of the phenomenological two-step hopping mechanism via the guanine base, the charge propagation occurs through a delocalization of the hole density along the base pair stack. Furthermore, the variations of the charge transfer with the position of the guanine base are explained by the impact of the base pair substitutions on the delocalized conduction channels.quantum filling | photoinduced hole transfer | stochastic surrogate Hamiltonian D espite a rather long history, investigations of excess charge carriers in DNA remain an area of intensive experimental and theoretical research (reviewed in refs. 1-3). This interest is mainly due to the relevance of the charge transfer (CT) phenomenon to the oxidation damage (4, 5) and to the potential application of DNA in nanoelectronics (6, 7). Experimentally, charge migration through DNA can be probed either by steady-state methods based on measurements of the damage ratio (8-10) or by time-resolved spectroscopic techniques (11)(12)(13)(14). The latter experimental approach was shown to be particularly efficient for monitoring charge motion in DNA hairpins (13). To carry out time-resolved spectroscopic experiments on these small DNA model systems, the opposite ends of the hairpin are capped with stilbene linkers S a and S b , serving as the hole donor and acceptor, respectively. It has been demonstrated that photoexcitation of S a results in the formation of a bound electron-hole pair initially localized on the hole donor. The separation of this pair occurs via the migration of the hole along the hairpin and the subsequent reaction of the positive charge with the stilbene acceptor. Kinetics of the hole arrival at S b , monitored by a second pulse, enable one to deduce the hole arrival rate, k a , and the quantum yield, Φ a , of the charge separation process.Hole migration along hairpins with less than three base pairs is discussed in terms of a single-step superexchange (15-18). In contrast, multistep sequential hopping is assumed to be responsible for charge propagation along longer hairpins (19-23). The competition between these two mechanisms leads to a distance dependence of the hole arrival rate given by:where N is the number of base pairs in the sequence, κ 1 and κ 2 are scaling factors, R 0 = 3:4 A is the mean interbase pair distance, β = 0:5 − 1:0 A −1 is the exponential falloff parameter for the superexchange mechanism (24-29), and η = 1:5 − 2:0 is the exponent of the power law characteristic f...

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confidence: 99%

Impact of a single base pair substitution on the charge transfer rate along short DNA hairpins

Renaud

Berlin

Ratner

2013

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

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“…Consistent with this finding, our studies using the naked RNA oligonucleotide did not reveal an effect of H 2 O 2 with or without Fe 2ϩ on G-quadruplex formation in solution. On the other hand, G residues in a G-quadruplex appear to be more likely oxidized than G residues in duplex DNA (80,81). 8-Oxoguanine in telomeric DNA influences the binding and activity of telomerase (82,83).…”

Section: Discussionmentioning

confidence: 99%

G-Quadruplex in the NRF2 mRNA 5′ Untranslated Region Regulates De Novo NRF2 Protein Translation under Oxidative Stress

Lee

Zhang

Strom

et al. 2017

Molecular and Cellular Biology

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Inhibition of protein synthesis serves as a general measure of cellular consequences of chemical stress. A few proteins are translated selectively and influence cell fate. How these proteins can bypass the general control of translation remains unknown. We found that low to mild doses of oxidants induce de novo translation of the NRF2 protein. Here we demonstrate the presence of a G-quadruplex structure in the 5= untranslated region (UTR) of NRF2 mRNA, as measured by circular dichroism, nuclear magnetic resonance, and dimethylsulfate footprinting analyses. Such a structure is important for 5=-UTR activity, since its removal by sequence mutation eliminated H 2 O 2 -induced activation of the NRF2 5= UTR. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics revealed elongation factor 1 alpha (EF1a) as a protein binding to the G-quadruplex sequence. Cells responded to H 2 O 2 treatment by increasing the EF1a protein association with NRF2 mRNA, as measured by RNA-protein interaction assays. The EF1a interaction with small and large subunits of ribosomes did not appear to change due to H 2 O 2 treatment, nor did posttranslational modifications, as measured by two-dimensional (2-D) Western blot analysis. Since NRF2 encodes a transcription factor essential for protection against tissue injury, our data have revealed a novel mechanism of cellular defense involving de novo NRF2 protein translation governed by the EF1a interaction with the G-quadruplex in the NRF2 5= UTR during oxidative stress.

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“…Given their potential role in acting as protective sinks against chromosomal oxidative damage [27][28][29], G-quadruplex architectures have been extensively examined for their charge conduction properties. In particular, adjacent guanines in G-quartets appear to be very effective nucleobases for excess electron transfer [30].…”

Section: Quantification Of Purine Lesions In G-quadruplex Nucleic Acimentioning

confidence: 99%

Radical-induced purine lesion formation is dependent on DNA helical topology

Terzidis

Prisecaru

Molphy

et al. 2016

Free Radical Research

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Herein we report the quantification of purine lesions arising from gamma-radiation sourced hydroxyl radicals (HO · ) on tertiary dsDNA helical forms of supercoiled (SC), open circular (OC), and linear (L) conformation, along with single-stranded folded and non-folded sequences of guanine-rich DNA in selected G-quadruplex structures. We identify that DNA helical topology and folding plays major, and unexpected, roles in the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxo-dA), along with tandem-type purine lesions 5 (mutTel24) were exposed to HO · radicals and purine lesions were then quantified via stable isotope dilution LC-MS/MS analysis. Purine oxidation in dsDNA follows L > OC ) SC indicating greater damage towards the extended B-DNA topology. Conversely, G-quadruplex sequences were significantly more resistant toward purine oxidation in their unfolded states as compared with G-tetrad folded topologies; this effect is confirmed upon comparative analysis of Tel22 ($50% solution folded) and mutTel24 ($90% solution folded). In an effort to identify the accessibly of hydroxyl radicals to quadruplex purine nucleobases, G-quadruplex solvent cavities were then modeled at 1.33 Å with evidence suggesting that folded G-tetrads may act as potential oxidant traps to protect against chromosomal DNA damage. ARTICLE HISTORY

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Charge Conduction Properties of a Parallel-Stranded DNA G-Quadruplex: Implications for Chromosomal Oxidative Damage

Cited by 40 publications

References 54 publications

Impact of a single base pair substitution on the charge transfer rate along short DNA hairpins

Impact of a single base pair substitution on the charge transfer rate along short DNA hairpins

G-Quadruplex in the NRF2 mRNA 5′ Untranslated Region Regulates De Novo NRF2 Protein Translation under Oxidative Stress

Radical-induced purine lesion formation is dependent on DNA helical topology

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