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.