ArticleNucleic acids research2011
The origin of genetic instability in CCTG repeats.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Rad51 strand invasion function is needed for its role in CCTG tetranucleotide DNA repeat contractions.microPublication biology · 2026Article
- Massive contractions of myotonic dystrophy type 2-associated CCTG tetranucleotide repeats occur via double-strand break repair with distinct requirements for DNA helicases.G3 (Bethesda, Md.) · 2024Article
- Structures and conformational dynamics of DNA minidumbbells in pyrimidine-rich repeats associated with neurodegenerative diseases.Computational and structural biotechnology journal · 2023Review
- Alternative DNA StructuresMicrobiology and molecular biology reviews : MMBR · 2021Review
- Minidumbbell structures formed by ATTCT pentanucleotide repeats in spinocerebellar ataxia type 10.Nucleic acids research · 2020Article
- A survey of recent unusual high-resolution DNA structures provoked by mismatches, repeats and ligand binding.Nucleic acids research · 2018Review
- Article
- Selective inhibition of MBNL1-CCUG interaction by small molecules toward potential therapeutic agents for myotonic dystrophy type 2 (DM2).Nucleic acids research · 2011Article
- The competing mini-dumbbell mechanism: new insights into CCTG repeat expansion.Signal transduction and targeted therapyArticle
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CCTG tetranucleotide repeat expansion is associated with a hereditary neurological disease called myotonic dystrophy type 2 (DM2). The underlying reasons that lead to genetic instability and thus repeat expansion during DNA replication remains elusive. Here, we have shown CCTG repeats have a high propensity to form metastable hairpin and dumbbell structures using high-resolution nuclear magnetic resonance (NMR) spectroscopy. When the repeat length is equal to three, a hairpin with a two-residue CT loop is formed. In addition to the hairpin, a dumbbell structure with two CT-loops is formed when the repeat length is equal to four. Nuclear Overhauser effect (NOE) and chemical shift data reveal both the hairpin and dumbbell structures contain a flexible stem comprising a C-bulge and a T·T mismatch. With the aid of single-site mutation samples, NMR results show these peculiar structures undergo dynamic conformational exchange. In addition to the intrinsic flexibility in the stem region of these structures, the exchange process also serves as an origin of genetic instability that leads to repeat expansion during DNA replication. The structural features provide important drug target information for developing therapeutics to inhibit the expansion process and thus the onset of DM2.
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