Sticky DNA: Self-Association Properties of Long GAA times TTC Repeats in R times R times Y Triplex Structures from Friedreich's Ataxia

A novel DNA structure, sticky DNA, is described for lengths of (GAA-TTC) sub(n), found in intron 1 of the frataxin gene of Friedreich's ataxia patients. Sticky DNA is formed by the association of two purine-purine-pyrimidine (R times R times Y) triplexes in negatively supercoiled plasmids at neutral pH. An excellent correlation was found between the lengths of (GAA times TTC) (>59 repeats): first, in FRDA patients, second, required to inhibit transcription in vivo and in vitro, and third, required to adopt the sticky conformation. Fourth, (GAAGGA times TCCTTC) sub(65), also found in intron 1, does not form sticky DNA, inhibit transcription, or associate with the disease. Hence, R times R times Y triplexes and/or sticky DNA may be involved 'in the etiology of FRDA.