Experimental Demonstration of T:(G:G:G:G):T Hexad and T:A:A:T TetradAlignments within a DNA Quadruplex Stem

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Abstract

A template-based approach was used to design unprecedented architectural motifs into a knownDNA framework. The structure formed by the sequence d(GCGGTTGGAT) in 0.1 M Na+ solution hasbeen determined using molecular dynamics simulations constrained by distance and dihedral restraintsderived from NMR experiments. The molecular topology has been previously observed for the sequenced(GCGGTGGAT) (Webba da Silva, M. (2003) Biochemistry 42, 14356-65). Insertion of a single thymineinto the double chain reversal formed by the segment GGTGG results in the unprecedented experimentaldemonstration of a T:(G:G:G:G):T hexad. The bi-stranded hexad results from the pairing alignment oftwo G(T-G) triads. Each triad results from recognition of the sheared edge of a guanine by the Watson-Crick edge of a thymine of the segment GGTTGG. The alignment is stabilized by base-stacking of thethymine to the sugar pucker of the preceding thymine. The latter is involved in formation of the T:A:A:Ttetrad alignment by forming a hydrogen bond with the free amino proton of a Watson-Crick alignedA:A mispair. We have thus established that residues in double chain reversal loops linking juxtaposedtetrads of a quadruplex stem may facilitate formation of yet unknown hydrogen bond alignments. Byemploying a systematic approach analysis of sequence motifs appearing in double chain reversals, bridgingtetrad layers should allow for the prediction of topologies and architectural motifs appearing in biologicallyrelevant genomic regions.
LanguageEnglish
JournalBiochemistry
Volume44
DOIs
Publication statusPublished - 10 Feb 2005

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G-Quadruplexes
Thymine
Hydrogen
Demonstrations
DNA
Guanine
Molecular Dynamics Simulation
Biochemistry
Sequence Analysis
Protons
Hydrogen bonds
Topology
Architectural design
Sugars
Molecular dynamics
Nuclear magnetic resonance
Computer simulation
Experiments

Cite this

@article{9d863ab2a60f4b2c9ce3b67925444618,
title = "Experimental Demonstration of T:(G:G:G:G):T Hexad and T:A:A:T TetradAlignments within a DNA Quadruplex Stem",
abstract = "A template-based approach was used to design unprecedented architectural motifs into a knownDNA framework. The structure formed by the sequence d(GCGGTTGGAT) in 0.1 M Na+ solution hasbeen determined using molecular dynamics simulations constrained by distance and dihedral restraintsderived from NMR experiments. The molecular topology has been previously observed for the sequenced(GCGGTGGAT) (Webba da Silva, M. (2003) Biochemistry 42, 14356-65). Insertion of a single thymineinto the double chain reversal formed by the segment GGTGG results in the unprecedented experimentaldemonstration of a T:(G:G:G:G):T hexad. The bi-stranded hexad results from the pairing alignment oftwo G(T-G) triads. Each triad results from recognition of the sheared edge of a guanine by the Watson-Crick edge of a thymine of the segment GGTTGG. The alignment is stabilized by base-stacking of thethymine to the sugar pucker of the preceding thymine. The latter is involved in formation of the T:A:A:Ttetrad alignment by forming a hydrogen bond with the free amino proton of a Watson-Crick alignedA:A mispair. We have thus established that residues in double chain reversal loops linking juxtaposedtetrads of a quadruplex stem may facilitate formation of yet unknown hydrogen bond alignments. Byemploying a systematic approach analysis of sequence motifs appearing in double chain reversals, bridgingtetrad layers should allow for the prediction of topologies and architectural motifs appearing in biologicallyrelevant genomic regions.",
author = "{Webba da Silva}, Mateus",
year = "2005",
month = "2",
day = "10",
doi = "10.1021/bi0478190",
language = "English",
volume = "44",
journal = "Biochemistry",
issn = "0006-2960",

}

TY - JOUR

T1 - Experimental Demonstration of T:(G:G:G:G):T Hexad and T:A:A:T TetradAlignments within a DNA Quadruplex Stem

AU - Webba da Silva, Mateus

PY - 2005/2/10

Y1 - 2005/2/10

N2 - A template-based approach was used to design unprecedented architectural motifs into a knownDNA framework. The structure formed by the sequence d(GCGGTTGGAT) in 0.1 M Na+ solution hasbeen determined using molecular dynamics simulations constrained by distance and dihedral restraintsderived from NMR experiments. The molecular topology has been previously observed for the sequenced(GCGGTGGAT) (Webba da Silva, M. (2003) Biochemistry 42, 14356-65). Insertion of a single thymineinto the double chain reversal formed by the segment GGTGG results in the unprecedented experimentaldemonstration of a T:(G:G:G:G):T hexad. The bi-stranded hexad results from the pairing alignment oftwo G(T-G) triads. Each triad results from recognition of the sheared edge of a guanine by the Watson-Crick edge of a thymine of the segment GGTTGG. The alignment is stabilized by base-stacking of thethymine to the sugar pucker of the preceding thymine. The latter is involved in formation of the T:A:A:Ttetrad alignment by forming a hydrogen bond with the free amino proton of a Watson-Crick alignedA:A mispair. We have thus established that residues in double chain reversal loops linking juxtaposedtetrads of a quadruplex stem may facilitate formation of yet unknown hydrogen bond alignments. Byemploying a systematic approach analysis of sequence motifs appearing in double chain reversals, bridgingtetrad layers should allow for the prediction of topologies and architectural motifs appearing in biologicallyrelevant genomic regions.

AB - A template-based approach was used to design unprecedented architectural motifs into a knownDNA framework. The structure formed by the sequence d(GCGGTTGGAT) in 0.1 M Na+ solution hasbeen determined using molecular dynamics simulations constrained by distance and dihedral restraintsderived from NMR experiments. The molecular topology has been previously observed for the sequenced(GCGGTGGAT) (Webba da Silva, M. (2003) Biochemistry 42, 14356-65). Insertion of a single thymineinto the double chain reversal formed by the segment GGTGG results in the unprecedented experimentaldemonstration of a T:(G:G:G:G):T hexad. The bi-stranded hexad results from the pairing alignment oftwo G(T-G) triads. Each triad results from recognition of the sheared edge of a guanine by the Watson-Crick edge of a thymine of the segment GGTTGG. The alignment is stabilized by base-stacking of thethymine to the sugar pucker of the preceding thymine. The latter is involved in formation of the T:A:A:Ttetrad alignment by forming a hydrogen bond with the free amino proton of a Watson-Crick alignedA:A mispair. We have thus established that residues in double chain reversal loops linking juxtaposedtetrads of a quadruplex stem may facilitate formation of yet unknown hydrogen bond alignments. Byemploying a systematic approach analysis of sequence motifs appearing in double chain reversals, bridgingtetrad layers should allow for the prediction of topologies and architectural motifs appearing in biologicallyrelevant genomic regions.

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DO - 10.1021/bi0478190

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