Interlocked mismatch-aligned arrowhead DNA motifs Journal Article


Authors: Kettani, A.; Bouaziz, S.; Skripkin, E.; Majumdar, A.; Wang, W. M.; Jones, R. A.; Patel, D. J.
Article Title: Interlocked mismatch-aligned arrowhead DNA motifs
Abstract: Background: Triplet repeat sequences are of considerable biological importance as the expansion of such tandem arrays can lead to the onset of a range of human diseases. Such sequences can self-pair via mismatch alignments to form higher order structures that have the potential to cause replication blocks, followed by strand slippage and sequence expansion, The all-purine d(GGA)(n) triplet repeat sequence is of particular interest because purines can align via G.G, A.A and G.A mismatch formation, Results: We have solved the structure of the uniformly C-13,N-15-labeled d(G1-G2-A3-G4-G5-A6-T7) sequence in 10 mM Na+ solution. This sequence adopts a novel twofold-symmetric duplex fold where interlocked V-shaped arrowhead motifs are aligned solely via interstrand G1.G4, G2.G5 and A3.A6 mismatch formation, The tip of the arrowhead motif is centered about the p-A3-p step, and symmetry-related local parallel-stranded duplex domains are formed by the G1-G2-A3 and G4-G5-A6 segments of partner strands. Conclusions: The purine-rich (GGA)(n) triplet repeat sequence is dispersed throughout the eukaryotic genome. Several features of the arrowhead duplex motif for the (GGA)(2) triplet repeat provide a unique scaffold for molecular recognition. These include the large localized bend in the sugar-phosphate backbones, the segmental parallel-stranded alignment of strands and the exposure of the Watson-Crick edges of several mismatched bases.
Keywords: human-disease; crystal-structure; nmr; sequences; repeats; base-pairs; dynamic mutations; uniform c-13,n-15-labeled dna; (gga) triplet repeat; mismatch alignments; parallel-stranded segments; v-shaped backbone; triple-helix formation; parallel-stranded dna; dot-a pairs
Journal Title: Structure
Volume: 7
Issue: 7
ISSN: 0969-2126
Publisher: Cell Press  
Date Published: 1999-07-15
Start Page: 803
End Page: 815
Language: English
ACCESSION: WOS:000081492400010
DOI: 10.1016/s0969-2126(99)80104-x
PROVIDER: wos
PUBMED: 10425682
Notes: Article -- Source: Wos
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  1. Dinshaw J Patel
    477 Patel