title: A small unstructured nucleic acid disrupts a trinucleotide repeat hairpin.
abstract: A variety of neurodegenerative disorders are associated with the expansion of trinucleotide repeat (TNR) sequences. These repetitive sequences are prone to adopting non-canonical structures, such as intrastrand stem-loop hairpins. Indeed, the formation and persistence of these hairpins during DNA replication and/or repair have been proposed as factors that facilitate TNR expansion. Given this proposed contribution of TNR hairpins to the expansion mechanism, disruption of such structures via strand invasion offers a potential means to negate the disease-initiating expansion. In this work, we investigated the strand invading abilities of a (CTG)(3) unstructured nucleic acid on a (CAG)(10) TNR hairpin. Using fluorescence, optical, and electrophoretic methods, instantaneous disruption of the (CAG)(10) hairpin by (CTG)(3) was observed at low temperatures. Additionally, we have identified three distinct duplex-like species that form between (CAG)(10) and (CTG)(3); these include 1, 2, or 3 (CTG)(3) sequences hybridized to (CAG)(10). The results presented here showcase (CTG)(3) as an invader of a TNR hairpin and suggest that unstructured nucleic acids could serve as a scaffold to design agents to prevent TNR expansion.
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, United States.
authors.forename: Amalia
authors.initials: A
authors.lastname: Avila-Figueroa
authors.forename: Douglas
authors.initials: D
authors.lastname: Cattie
authors.forename: Sarah
authors.initials: S
authors.lastname: Delaney
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000648:ultrastructure; D055029:Inverted Repeat Sequences; D009690:Nucleic Acid Conformation; D013816:Thermodynamics; D018911:Trinucleotide Repeats
chemical_list: D004247:DNA