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DNA triplexes and Friedreich ataxia
Author(s) -
Wells Robert D.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-097857
Subject(s) - frataxin , ataxia , gene silencing , genetics , biology , trinucleotide repeat expansion , dna , heterochromatin , gene , microbiology and biotechnology , chromatin , iron binding proteins , neuroscience , allele
Friedreich ataxia, the most common in herited ataxia, is caused by the transcriptional silencing of the FXN gene, which codes for the 210 amino acid frataxin, a mitochondrial protein involved in iron‐ sulfur cluster biosynthesis. The expansion of the GAATTC tract in intron 1 to as many as 1700 repeats elicits the transcriptional silencing by the formation of non‐B DNA structures (triplexes or sticky DNA), the formation of a persistent DNA‐RNA hybrid, or hetero chromatin formation. The triplex (sticky DNA) adopted by the long repeat sequence also elicits pro found mutagenic, genetic instability, and recombination behaviors. Early stage therapeutic investigations involving polyamides or histone deacetylase inhibitors are being pursued. Friedreich ataxia may be one of the most thoroughly studied hereditary neurological dis ease from a pathophysiological standpoint.— Wells, R. D. DNA triplexes and Friedreich ataxia. FASEB J. 22, 1625–1634 (2008)