Amalia Avila-Figueroa, Douglas Cattie, Sarah Delaney
Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, United States.
Biochemical and biophysical research communications 2011 Oct 7A 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. Copyright © 2011 Elsevier Inc. All rights reserved.
Amalia Avila-Figueroa, Douglas Cattie, Sarah Delaney. A small unstructured nucleic acid disrupts a trinucleotide repeat hairpin. Biochemical and biophysical research communications. 2011 Oct 7;413(4):532-6
PMID: 21924238
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