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Papers In Press, published online ahead of print August 2, 2002
Center for Genome Research, Institute of Biosciences & Technology, Houston, TX 77030
Corresponding Author: rwells{at}ibt.tamu.edu
Friedreichs ataxia (FRDA) is caused by the massive expansion of GAATTC repeats in intron 1 of the frataxin (X25) gene. Our prior investigations showed that long GAATTC repeats formed very stable triplex structures which caused two repeat tracts to adhere to each other (sticky DNA). This process was dependent on negative supercoiling and the presence of divalent metal ions. Herein, we have investigated the formation of sticky DNA from plasmid monomers and dimers; sticky DNA is formed only when two tracts of sufficiently long (GAATTC)n (n = 59 270) are present in a single plasmid DNA and are in the direct repeat orientation. If the inserts are in the indirect (inverted) repeat orientation, no sticky DNA was observed. Furthermore, kinetic studies support the intramolecular nature of sticky DNA formation. Electron microscopy (EM) investigations also provide strong data for sticky DNA as a single long triplex. Hence, these results give new insights into our understanding of the capacity of sticky DNA to inhibit transcription and thereby reduce the level of frataxin protein as related to the etiology of FRDA.
J. Biol. Chem, 10.1074/jbc.M205209200
Submitted on May 28, 2002
Revised on July 30, 2002
Accepted on August 1, 2002
Sticky DNA, a long GAA5GAA5TTC triplex which is formed intramolecularly, in the sequence of intron 1 of the Frataxin gene
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