ArticleScientific reports2015
Large expansion of CTG•CAG repeats is exacerbated by MutSβ in human cells.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Expanding repeats, expanding impact: Somatic instability in myotonic dystrophy type 1.Journal of neuromuscular diseases · 2026Review
- MSH2 is not required for either maintenance of DNA methylation or repeat contraction at the FMR1 locus in fragile X syndrome or the FXN locus in Friedreich's ataxia.Epigenetics & chromatin · 2025Article
- Structural and Dynamical Properties of Nucleic Acid Hairpins Implicated in Trinucleotide Repeat Expansion Diseases.Biomolecules · 2024Review
- Cas9 nickase-mediated contractions of CAG/CTG repeats are transcription-dependent and replication-independent.NAR molecular medicine · 2024Article
- Article
- Article
- Ago2 and a miRNA reduce Topoisomerase 1 for enhancing DNA cleavage in antibody diversification by activation-induced cytidine deaminase.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Review
- Somatic CAG expansion in Huntington's disease is dependent on the MLH3 endonuclease domain, which can be excluded via splice redirection.Nucleic acids research · 2021Article
- DNA Mismatch Repair and its Role in Huntington's Disease.Journal of Huntington's disease · 2021Review
- Modifiers of CAG/CTG Repeat Instability: Insights from Mammalian Models.Journal of Huntington's disease · 2021Review
- Modifiers of Somatic Repeat Instability in Mouse Models of Friedreich Ataxia and the Fragile X-Related Disorders: Implications for the Mechanism of Somatic Expansion in Huntington's Disease.Journal of Huntington's disease · 2021Review
- New developments in Huntington's disease and other triplet repeat diseases: DNA repair turns to the dark side.Neuronal signaling · 2020Review
- Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities.Nature reviews. Neurology · 2020Review
- HDAC3 deacetylates the DNA mismatch repair factor MutSβ to stimulate triplet repeat expansions.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Functional Consequences of Eukaryotic Topoisomerase 1 Interaction with G-Quadruplex DNA.Genes · 2020Review
- A slipped-CAG DNA-binding small molecule induces trinucleotide-repeat contractions in vivo.Nature genetics · 2020Article
- A small molecule kicks repeat expansion into reverse.Nature genetics · 2020Article
- RNA-DNA hybrids promote the expansion of Friedreich's ataxia (GAA)n repeats via break-induced replication.Nucleic acids research · 2018Article
- The central role of DNA damage and repair in CAG repeat diseases.Disease models & mechanisms · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trinucleotide repeat expansion disorders (TRED) are caused by genomic expansions of trinucleotide repeats, such as CTG and CAG. These expanded repeats are unstable in germline and somatic cells, with potential consequences for disease severity. Previous studies have demonstrated the involvement of DNA repair proteins in repeat instability, although the key factors affecting large repeat expansion and contraction are unclear. Here we investigated these factors in a human cell model harboring 800 CTG•CAG repeats by individually knocking down various DNA repair proteins using short interfering RNA. Knockdown of MSH2 and MSH3, which form the MutSβ heterodimer and function in mismatch repair, suppressed large repeat expansions, whereas knockdown of MSH6, which forms the MutSα heterodimer with MSH2, promoted large expansions exceeding 200 repeats by compensatory increases in MSH3 and the MutSβ complex. Knockdown of topoisomerase 1 (TOP1) and TDP1, which are involved in single-strand break repair, enhanced large repeat contractions. Furthermore, knockdown of senataxin, an RNA/DNA helicase which affects DNA:RNA hybrid formation and transcription-coupled nucleotide excision repair, exacerbated repeat instability in both directions. These results indicate that DNA repair factors, such as MutSβ play important roles in large repeat expansion and contraction, and can be an excellent therapeutic target for TRED.
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