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Structural and Dynamical Properties of Nucleic Acid Hairpins Implicated in Trinucleotide Repeat Expansion Diseases

Authors :
Feng Pan
Pengning Xu
Christopher Roland
Celeste Sagui
Keith Weninger
Source :
Biomolecules, Vol 14, Iss 10, p 1278 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Dynamic mutations in some human genes containing trinucleotide repeats are associated with severe neurodegenerative and neuromuscular disorders—known as Trinucleotide (or Triplet) Repeat Expansion Diseases (TREDs)—which arise when the repeat number of triplets expands beyond a critical threshold. While the mechanisms causing the DNA triplet expansion are complex and remain largely unknown, it is now recognized that the expandable repeats lead to the formation of nucleotide configurations with atypical structural characteristics that play a crucial role in TREDs. These nonstandard nucleic acid forms include single-stranded hairpins, Z-DNA, triplex structures, G-quartets and slipped-stranded duplexes. Of these, hairpin structures are the most prolific and are associated with the largest number of TREDs and have therefore been the focus of recent single-molecule FRET experiments and molecular dynamics investigations. Here, we review the structural and dynamical properties of nucleic acid hairpins that have emerged from these studies and the implications for repeat expansion mechanisms. The focus will be on CAG, GAC, CTG and GTC hairpins and their stems, their atomistic structures, their stability, and the important role played by structural interrupts.

Details

Language :
English
ISSN :
2218273X
Volume :
14
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Biomolecules
Publication Type :
Academic Journal
Accession number :
edsdoj.4512aaf1d9174391b6618094e79e6f79
Document Type :
article
Full Text :
https://doi.org/10.3390/biom14101278