title: DNA triplexes and Friedreich ataxia.
abstract: Friedreich ataxia, the most common inherited 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 GAA x TTC 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 x RNA hybrid, or heterochromatin formation. The triplex (sticky DNA) adopted by the long repeat sequence also elicits profound 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 disease from a pathophysiological standpoint.
authors.affiliation: Center for Genome Research, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, The Texas Medical Center, 2121 W. Holcombe Blvd., Houston, TX 77030-3303, USA. rwells@ibt.tamhsc.edu
authors.forename: Robert D
authors.initials: RD
authors.lastname: Wells
mesh_terms: D004247:DNA / Q000737:chemistry*; D005621:Friedreich Ataxia / Q000188:drug therapy / Q000235:genetics*; D020868:Gene Silencing; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009690:Nucleic Acid Conformation; D009757:Nylons
chemical_list: D056572:Histone Deacetylase Inhibitors; D009757:Nylons; D004247:DNA