Conformation and dynamics of Z-DNA oligomer duplex of d[(CG)<sub>3</sub>TATA(CG)<sub>3</sub>] in solution

Ikuta, Satoshi; Wang, Yu-Sen

doi:10.1093/nar/17.11.4131

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…In either high or low salt the tm determined at every DNA concentration examined never deviated outside the experimental uncertainty. In contrast to what was observed, self-complementary DNA oligomers which form bimolecular bulged duplexes clearly display bi-phasic melting curves and concentration dependent tm values over a similar range in DNA concentration (10,26,27). From these findings combined with results of gel electrophoresis of the concentrated DNA solutions in high and low salt, (see MATERIALS AND METHODS), we confidently assume for the remainder of the analysis that all of the oligomers of this study preferentially exist as uni-molecular hairpins.…”

Section: Hairpinsmentioning

confidence: 59%

B to Z transitions of the short DNA hairpins formed from the oligomer sequences: d[(CG)₃×₄(CG)₃] (X = A, T, G, C)

Amaratunga¹,

Pančoška²,

Paner³

et al. 1990

Nucl Acids Res

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Circular Dichroism (CD) spectra were collected as a function of sodium perchlorate concentration [NaClO4] for the set of DNA hairpins formed from the oligomer sequences d[(CG)3X4(CG)3] where X = A, T, G or C. Over the range in salt concentration from 0 to 4.0 M NaClO4, the CD spectra invert in a manner characteristic of the B to Z transition. A factor analysis routine is described and employed to determine the least number of basis spectra required to fit the measured spectra of each hairpin over the entire salt range examined. In every case, linear combinations of only two sub-spectra fit the experimental spectra of the hairpins with greater than 98% accuracy, indicating the spectrally monitored structural transitions are two-state. From the relative weights of the individual sub-spectra, B-Z transition curves are constructed. The transitions are analyzed in terms of a simple two-state equilibrium model which yields an evaluation of the transition free-energy, delta GB-Z, as a function of NaClO4 concentration. At 1.0 M NaClO4 and 21 degrees C, delta GB-Z = 5.4, 4.9, 3.6 and 2.3 kcal/mole for the G4, T4, A4 and C4 loop hairpins, respectively.

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Section: Hairpinsmentioning

confidence: 59%

B to Z transitions of the short DNA hairpins formed from the oligomer sequences: d[(CG)₃×₄(CG)₃] (X = A, T, G, C)

Amaratunga¹,

Pančoška²,

Paner³

et al. 1990

Nucl Acids Res

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“…Evidence for internal oscillatory motions in DNA was recognized by using fluorescence intercalators bound to the helix (Wahl et al, 1970). NMR has been used to observe internal motions in the Band Z-conformations of DNA oligomers (Mirau et al, 1985;Ikuta & Wang, 1989). Spin labeling of bases with nitroxides provides a means of observing the nature of these motions.…”

mentioning

confidence: 99%

Base dynamics of local Z-DNA conformations as detected by electron paramagnetic resonance with spin-labeled deoxycytidine analogs

Strobel¹,

Keyes²,

Bobst³

1990

Biochemistry

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Conformation detection and base dynamics of spin-labeled Z-DNA have been investigated by electron paramagnetic resonance (EPR) spectroscopy. The two synthesized and characterized probes used in this study were C(5)-nitroxide-labeled 2'-deoxycytidine 5'-triphosphates, pppDCAT and pppDCAVAT, which serve as suitable substrates for Micrococcus luteus DNA polymerase. Enzymatic incorporation of these probes into (dG-dC)n yields the EPR-active alternating copolymers (dG-dC,DCAT)n and (dG-dC,-DCAVAT)n. These polymers assume typical B- and Z-DNA conformations under respective low (0.1 M NaCl) and high (4.5 M NaCl) salt conditions, as evidenced by their UV-circular dichroism spectra. The EPR line shape of (dG-dC,DCAT)n in Z-form is unique and significantly different from the B-form EPR spectrum. A similar observation is made for (dG-dC,DCAVAT)n. Thus, the EPR line shapes of these spin-labeled DNAs are indicative of their local conformations. The EPR spectra, analyzed with a previously published motional model [Kao, S.-C., Polnaszek, C.F., Toppin, C.R., & Bobst, A.M. (1983) Biochemistry 22, 5563-5568], indicate tau perpendicular values of 4 and 7 ns for the B- and Z-forms, respectively. Therefore, the base dynamics of Z-DNA are about two times slower than in B-DNA.

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“…In B-DNA, all deoxyriboses are in anti conformation while Z-DNA has an alternating syn-anti backbone. These differences give rise to unique NMR spectra, mainly,due to the effect of conformation on the chemical shifts of the H1' protons and also the conformational requirements [94][95][96] . In the case of poly d(CG), the most notable observation is that the Z conformation displays strong nOe cross peak correlations between the guanine H8 and H1′ 95 .…”

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confidence: 99%

The effect of C8-arylguanine adducts on B/Z-DNA equilibrium: Implications in aryl hydrazine carcinogenesis

Vongsutilers¹

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The Effect of C8-Arylguanine Adducts on B/Z-DNA Equilibrium: Implications in Aryl Hydrazine Carcinogenesis Vorasit Vongsutilers Aryl hydrazines and related compounds have been shown to be carcinogenic but the mechanism is still unclear. C8-Arylguanine adducts, formed from oxidative metabolites of aryl hydrazines, are suspected to be the cause of carcinogenesis. Z-DNA formation facilitated by the aryl adduct are among the potential mechanisms and has been investigated in this study. Z-DNA may be involved in carcinogenesis as several studies have indicated that Z-DNA may play an important role in gene expression and to induce mutagenic genetic deletions. C8-Arylguanine adducts may cause carcinogenesis by promoting the formation of Z-DNA which in turn disturbing gene regulation and leading to mutagenesis. To investigate this hypothesis, we have set out to 1) study the effect of aryl adducts formed from carcinogenic aryl hydrazines on B/Z-DNA equilibrium and 2) seek the relevancy between Z-DNA formation and aryl hydrazine carcinogenesis. Here, alternating CG decamers containing C8-arylguanine modifications (d(CGCGCG*CGCG) 2 , G* = C8-tolyl, C8-carboxyphenyl, C8-methoxymethylphenyl, or C8-hydroxymethylphenyl guanine), were prepared through Suzuki coupling and phosphoramidite chemistry. The effect of the aryl adducts on the B/Z-DNA equilibrium were determined by CD and NMR analysis. The experimental results supported by computational study have suggested that all of the aryl modifications examined facilitate B-Z transition by destabilizing the B conformation and/or stabilizing the Z conformation relative to the corresponding unmodified oligonucleotide. Among the aryl adducts, C8carboxyphenyl adduct has been shown to be best at facilitating B-Z transition followed by C8-phenyl, C8-methoxymethylphenyl, C8-hydroxymethylphenyl, and C8-tolyl respectively. The effect of aryl adducts on B-Z transition is generally correlated with the reported V79 mutagenicity of the aryl hydrazines precursors. This preliminary study has suggested that Z-DNA may be involved or plays a role in aryl hydrazine carcinogenesis. iii ACKNOWLEDGEMENT First of all, I would like to express my thanks to Dr. Peter M. Gannett, my advisor, for his guidance during my journey as a graduate student. His remarkable knowledge in various fields and more importantly, his understanding and encouragement, have greatly helped me get through hardship in my study.

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Conformation and dynamics of Z-DNA oligomer duplex of d[(CG)₃TATA(CG)₃] in solution

Cited by 4 publications

References 31 publications

B to Z transitions of the short DNA hairpins formed from the oligomer sequences: d[(CG)₃×₄(CG)₃] (X = A, T, G, C)

B to Z transitions of the short DNA hairpins formed from the oligomer sequences: d[(CG)₃×₄(CG)₃] (X = A, T, G, C)

Base dynamics of local Z-DNA conformations as detected by electron paramagnetic resonance with spin-labeled deoxycytidine analogs

The effect of C8-arylguanine adducts on B/Z-DNA equilibrium: Implications in aryl hydrazine carcinogenesis

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Conformation and dynamics of Z-DNA oligomer duplex of d[(CG)3TATA(CG)3] in solution

Cited by 4 publications

References 31 publications

B to Z transitions of the short DNA hairpins formed from the oligomer sequences: d[(CG)3×4(CG)3] (X = A, T, G, C)

B to Z transitions of the short DNA hairpins formed from the oligomer sequences: d[(CG)3×4(CG)3] (X = A, T, G, C)

Base dynamics of local Z-DNA conformations as detected by electron paramagnetic resonance with spin-labeled deoxycytidine analogs

The effect of C8-arylguanine adducts on B/Z-DNA equilibrium: Implications in aryl hydrazine carcinogenesis

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Conformation and dynamics of Z-DNA oligomer duplex of d[(CG)₃TATA(CG)₃] in solution

B to Z transitions of the short DNA hairpins formed from the oligomer sequences: d[(CG)₃×₄(CG)₃] (X = A, T, G, C)

B to Z transitions of the short DNA hairpins formed from the oligomer sequences: d[(CG)₃×₄(CG)₃] (X = A, T, G, C)