HAIRPIN PROPERTIES OF SINGLE-STRANDED-DNA CONTAINING A GC-RICH TRIPLET REPEAT - (CTG)(15)

Although triplet repeat DNA sequences are scattered throughout the hum an genome, their biological function remains obscure, To aid in correl ating potential structures of these nucleic acids with their function, we propose their classification based on the presence or absence of a palindromic dinucleotide within the triplet, the G+C content, and the presence or absence of a homopolymer, Five classes of double-stranded (ds) triplet repeats are distinguished, Class I repeats, which are de fined by the presence of a GC or CG palindrome, have the lowest base s tacking energies, exhibit the lowest rates of slippage synthesis [Schl otterer and Tautz (1992) Nucleic Acids Res., 20, 211] and are uniquely associated with triplet repeat expansion diseases. The six single-str anded (ss) triplet repeats within Class I also have the potential to f orm hairpin structures, as determined by energy minimization, To explo re the possibility of hairpin formation by ss Class I triplet repeats, studies were performed with a ss oligonucleotide containing 15 protot ypic CTG repeats [ss (CTG)(15)]. Electrophoretic, P1 nuclease and KMnO 4 oxidation data demonstrate that ss (CTG)(15) forms a hairpin contain ing base paired and/or stacked thymines in the stem, Potential functio ns of hairpins containing Class I triplet repeats are discussed with r espect to protein translation and mRNA splicing, Further, potential ro les of hairpin structures in triplet repeat expansion events are discu ssed.