Interlocked mismatch-aligned arrowhead DNA motifs

Abdelali Kettani, Serge Bouaziz, Eugene Skripkin, Ananya Majumdar, Weimin Wang, Roger A. Jones, Dinshaw J. Patel

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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·G1 A·A and G·A mismatch formation. Results: We have solved the structure of the uniformly 13C,15N-labeled d(G1-G2-A3-G4-GS- 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·G41 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.

Original languageEnglish (US)
Pages (from-to)803-815
Number of pages13
JournalStructure
Volume7
Issue number7
DOIs
StatePublished - Jul 15 1999

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Keywords

  • (GGA) triplet repeat
  • Mismatch alignments
  • N-labeled DNA
  • Parallel-stranded segments
  • Uniform C
  • V-shaped backbone

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