The Structure of Dna

Watson, James D.; Crick, Francis

doi:10.1101/sqb.1953.018.01.020

Cited by 889 publications

(347 citation statements)

References 14 publications

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“…2d and Extended Data Fig. 4) 33 and a G•T enol /U enol →G enol •T/U transition state barrier <9-10 kcal mol −1 (pre-exponential factor = k B T h −1(34) and κ = 1) that is in good agreement with values (≈11.5 kcal mol −1 ) reported using computational methods 25 . These results establish the existence of G•T enol /U enol and G enol •T/U in an ultra-fast equilibrium, each of which can potentially contribute to replication and translation errors.…”

Section: Sequence-dependent Genol•t/u⇌g•tenol/uenolsupporting

confidence: 83%

“…These differences may be attributed to the electron-donating methyl group in dT which destabilizes dT enol relative to rU enol(32) . The RD data also allowed us to estimate a lower bound for the fast tautomeric exchange rate

k_{t} = k_{G^{enol} \to T^{enol}} + k_{T^{enol} \to G^{enol}}

>≈500,000-1,000,000 s −1 (Fig. 2d and Extended Data Fig.…”

Section: Sequence-dependent Genol•t/u⇌g•tenol/uenolmentioning

confidence: 99%

“…In their paper describing the structure of the DNA double helix 1 , Watson and Crick proposed that if nucleotide bases adopted their energetically unfavorable tautomeric forms, mismatches (Fig. 1a) could pair up in a Watson-Crick-like (WC-like) geometry (Fig.…”

mentioning

confidence: 99%

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Dynamic basis for dG•dT misincorporation via tautomerization and ionization

Kimsey

Szymanski

Zahurancik

et al. 2018

Nature

133

183

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Tautomeric and anionic Watson-Crick-like mismatches play important roles in replication and translation errors through mechanisms that are not fully understood. Using NMR relaxation dispersion, we resolved a sequence-dependent kinetic network connecting G•T/U wobbles with three distinct Watson-Crick mismatches consisting of two rapidly exchanging tautomeric species (Genol•T/U⇌G•Tenol/Uenol; population <0.4%) and one anionic species (G•T−/U−; population ≈0.001% at neutral pH). Inserting the sequence-dependent tautomerization/ionization step into a minimal kinetic mechanism for correct incorporation during replication following initial nucleotide binding leads to accurate predictions of dG•dT misincorporation probability across different polymerases, pH conditions, and for a chemically modified nucleotide, and provides mechanisms for sequence-dependent misincorporation. Our results indicate that the energetic penalty for tautomerization/ionization accounts for ≈10−2−10−3–fold discrimination against misincorporation, which proceeds primarily via tautomeric dGenol•dT and dG•dTenol with contributions from anionic dG•dT− dominating at pH ≥8.4 or for some mutagenic nucleotides.

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Section: Sequence-dependent Genol•t/u⇌g•tenol/uenolsupporting

confidence: 83%

k_{t} = k_{G^{enol} \to T^{enol}} + k_{T^{enol} \to G^{enol}}

>≈500,000-1,000,000 s −1 (Fig. 2d and Extended Data Fig.…”

Section: Sequence-dependent Genol•t/u⇌g•tenol/uenolmentioning

confidence: 99%

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Dynamic basis for dG•dT misincorporation via tautomerization and ionization

Kimsey

Szymanski

Zahurancik

et al. 2018

Nature

133

183

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“…25 This GC-rich element is located in the proximity of a nuclease hypersensitive region, 32 which has been shown to be dynamic in nature and capable of adopting paranemic structures or non-B-DNA conformations. 33 In particular, guanine-rich sequences can adopt specific intramolecular DNA secondary structures termed Gquadruplexes ( Figure 1B). 34 Guanine-rich DNA sequences predisposed to the formation of G-quadruplexes have been identified in the telomeres of virtually all eukaryotic organisms, 35 in immunoglobulin switch regions, 36 and in the promoter regions of several growth-related genes.…”

Section: Introductionmentioning

confidence: 99%

Deconvoluting the Structural and Drug-Recognition Complexity of the G-Quadruplex-Forming Region Upstream of the bcl-2 P1 Promoter

2006

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The human bcl-2 gene contains a GC-rich region upstream of the P1 promoter that has been shown to be critically involved in the regulation of bcl-2 gene expression. We have demonstrated that the guanine-rich strand of the DNA in this region can form any one of three distinct intramolecular Gquadruplex structures. Mutation and deletion analysis permitted isolation and identification of three overlapping DNA sequences within this element that formed the three individual G-quadruplexes. Each of these was characterized using nondenaturing gel analysis, DMS footprinting, and circular dichroism. The central G-quadruplex, which is the most stable, forms a mixed parallel/antiparallel structure consisting of three tetrads connected by loops of one, seven, and three bases. Three different G-quadruplex-interactive agents were found to further stabilize these structures, with individual selectivity toward one or more of these G-quadruplexes. Collectively, these results suggest that the multiple G-quadruplexes identified in the promoter region of the bcl-2 gene are likely to play a similar role to the G-quadruplexes in the c-myc promoter in that their formation could serve to modulate gene transcription. Last, we demonstrate that the complexity of the G-quadruplexes in the bcl-2 promoter extends beyond the ability to form any one of three separate G-quadruplexes to each having the capacity to form either three or six different loop isomers. These results are discussed in relation to the biological significance of this G-quadruplex-forming element in modulation of bcl-2 gene expression and the inherent complexity of the system where different G-quadruplexes and loop isomers are possible.

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“…Since the discovery of the DNA double helix structure in 1953 many researchers have been intrigued not only by its role and the processes involved in storing genetic information but also by its utilization as a building block for nanostructures [1]. This trend has been fuelled by the introduction of automated solid phase synthesis, polymerase chain reaction and molecular cloning techniques allowing to produce oligonucleotides (ODNs) and long nucleic acid strands and make them available for a wide scientific community at an affordable price or effort.…”

Section: Introductionmentioning

confidence: 99%

Drug delivery systems based on nucleic acid nanostructures

Vries

Zhang

Herrmann

2013

Journal of Controlled Release

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a b s t r a c t a r t i c l e i n f oThe field of DNA nanotechnology has progressed rapidly in recent years and hence a large variety of 1D-, 2D-and 3D DNA nanostructures with various sizes, geometries and shapes is readily accessible. DNA-based nanoobjects are fabricated by straight forward design and self-assembly processes allowing the exact positioning of functional moieties and the integration of other materials. At the same time some of these nanosystems are characterized by a low toxicity profile. As a consequence, the use of these architectures in a biomedical context has been explored. In this review the progress and possibilities of pristine nucleic acid nanostructures and DNA hybrid materials for drug delivery will be discussed. For the latter class of structures, a distinction is made between carriers with an inorganic core composed of gold or silica and amphiphilic DNA block copolymers that exhibit a soft hydrophobic interior.

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The Structure of Dna

Cited by 889 publications

References 14 publications

Dynamic basis for dG•dT misincorporation via tautomerization and ionization

Dynamic basis for dG•dT misincorporation via tautomerization and ionization

Deconvoluting the Structural and Drug-Recognition Complexity of the G-Quadruplex-Forming Region Upstream of the bcl-2 P1 Promoter

Drug delivery systems based on nucleic acid nanostructures

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