DNA triplex structures in neurodegenerative disorder, Friedreich’s ataxia.
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Date
2012-07
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Abstract
It is now established that a small fraction of genomic DNA does adopt the non-canonical B-DNA structure or
‘unusual’ DNA structure. The unusual DNA structures like DNA-hairpin, cruciform, Z-DNA, triplex and tetraplex are
represented as hotspots of chromosomal breaks, homologous recombination and gross chromosomal rearrangements
since they are prone to the structural alterations. Friedreich’s ataxia (FRDA), the autosomal recessive degenerative
disorder of nervous and muscles tissue, is caused by the massive expansion of (GAA) repeats that occur in the first
intron of Frataxin gene X25 on chromosome 9q13-q21.1. The purine strand of the DNA in the expanded (GAA) repeat
region folds back to form the (R∙R*Y) type of triplex, which further inhibits the frataxin gene expression, and this
clearly suggests that the shape of DNA is the determining factor in the cellular function. FRDA is the only disease
known so far to be associated with DNA triplex. Structural characterization of GAA-containing DNA triplexes using
some simple biophysical methods like UV melting, UV absorption, circular dichroic spectroscopy and electrophoretic
mobility shift assay are discussed. Further, the clinical aspects and genetic analysis of FRDA patients who carry
(GAA) repeat expansions are presented. The potential of some small molecules that do not favour the DNA triplex
formation as therapeutics for FRDA are also briefly discussed.
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Keywords
DNA triple helix, Friedreich’s ataxia, (GAA) repeats, triplet repeat expansion (TRE) neurodegenerative disorder
Citation
Rajeswari Moganty R. DNA triplex structures in neurodegenerative disorder, Friedreich’s ataxia. Journal of Biosciences. 2012 July; 37 (3): 519-532.