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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.
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Mechanics of dynamic and deformable DNA nanostructures
In DNA nanotechnology, DNA molecules are designed, engineered, and assembled into arbitrary-shaped architectures with predesigned functions. Static DNA assemblies often have delicate designs with structural rigidity to overcome thermal fluctuations. Dynamic structures reconfigure in response to external cues, which have been explored to create functional nanodevices for environmental sensing and other applications. However, the precise control of reconfiguration dynamics has been a challenge due partly to flexible single-stranded DNA connections between moving parts. Deformable structures are special dynamic constructs with deformation on double-stranded parts and single-stranded hinges during transformation. These structures often have better control in programmed deformation. However, related deformability and mechanics including transformation mechanisms are not well understood or documented. In this review, we summarize the development of dynamic and deformable DNA nanostructures from a mechanical perspective. We present deformation mechanisms such as single-stranded DNA hinges with lock-and-release pairs, jack edges, helicity modulation, and external loading. Theoretical and computational models are discussed for understanding their associated deformations and mechanics. We elucidate the pros and cons of each model and recommend design processes based on the models. The design guidelines should be useful for those who have limited knowledge in mechanics as well as expert DNA designers.
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- PAR ID:
- 10440527
- Date Published:
- Journal Name:
- Chemical Science
- Volume:
- 14
- Issue:
- 30
- ISSN:
- 2041-6520
- Page Range / eLocation ID:
- 8018 to 8046
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D3SC01793A
