Sticky DNA: Self-association properties of long GAA center dot TTC repeatsin R center dot R center dot Y triplex structures from Friedreich's ataxia

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