Ulster University Logo

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

Webba da Silva, Mateus (2005) Experimental Demonstration of T:(G:G:G:G):T Hexad and T:A:A:T TetradAlignments within a DNA Quadruplex Stem. Biochemistry, 44 . [Journal article]

[img] PDF - Accepted Version
Indefinitely restricted to Repository staff only.

786kB

DOI: 10.1021/bi0478190

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.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute > Genomic Medicine > Transcriptional Regulation & Epigenetics
Biomedical Sciences Research Institute > Genomic Medicine
Biomedical Sciences Research Institute
ID Code:18296
Deposited By: Dr Mateus Webba da Silva
Deposited On:03 May 2011 10:11
Last Modified:09 Dec 2015 10:56

Repository Staff Only: item control page