ArticleNucleic acids research2012
MutSβ and histone deacetylase complexes promote expansions of trinucleotide repeats in human cells.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 64 citations in OpenAlex.
- Mismatch repair MLH complexes make distinct contributions to post-replicative mismatch repair versus trinucleotide repeat expansions.bioRxiv : the preprint server for biology · 2026Article
- 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
- Cas9 nickase-mediated contractions of CAG/CTG repeats are transcription-dependent and replication-independent.NAR molecular medicine · 2024Article
- Mutant huntingtin protein induces MLH1 degradation, DNA hyperexcision, and cGAS-STING-dependent apoptosis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- 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
- MSH2-MSH3 promotes DNA end resection during homologous recombination and blocks polymerase theta-mediated end-joining through interaction with SMARCAD1 and EXO1.Nucleic acids research · 2023Article
- Overview of the Complex Relationship between Epigenetics Markers, CTG Repeat Instability and Symptoms in Myotonic Dystrophy Type 1.International journal of molecular sciences · 2022Review
- Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing.Human molecular genetics · 2022Article
- Genomic Instability and Cancer Risk Associated with Erroneous DNA Repair.International journal of molecular sciences · 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
- Modifiers of CAG/CTG Repeat Instability: Insights from Mammalian Models.Journal of Huntington's disease · 2021Review
- FAN1, a DNA Repair Nuclease, as a Modifier of Repeat Expansion Disorders.Journal of Huntington's disease · 2021Review
- DNA Mismatch Repair and its Role in Huntington's Disease.Journal of Huntington's disease · 2021Review
- Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities.Nature reviews. Neurology · 2020Review
- Article
- 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
- All three mammalian MutL complexes are required for repeat expansion in a mouse cell model of the Fragile X-related disorders.PLoS genetics · 2020Article
- A Variation in FGF14 Is Associated with Downbeat Nystagmus in a Genome-Wide Association Study.Cerebellum (London, England) · 2020Article
- The G-rich Repeats inGenetics · 2018Article
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trinucleotide repeat (TNR) expansions cause at least 17 heritable neurological diseases, including Huntington's disease. Expansions are thought to arise from abnormal processing of TNR DNA by specific trans-acting proteins. For example, the DNA repair complex MutSβ (MSH2-MSH3 heterodimer) is required in mice for on-going expansions of long, disease-causing alleles. A distinctive feature of TNR expansions is a threshold effect, a narrow range of repeat units (∼30-40 in humans) at which mutation frequency rises dramatically and disease can initiate. The goal of this study was to identify factors that promote expansion of threshold-length CTG•CAG repeats in a human astrocytic cell line. siRNA knockdown of the MutSβ subunits MSH2 or MSH3 impeded expansions of threshold-length repeats, while knockdown of the MutSα subunit MSH6 had no effect. Chromatin immunoprecipitation experiments indicated that MutSβ, but not MutSα, was enriched at the TNR. These findings imply a direct role for MutSβ in promoting expansion of threshold-length CTG•CAG tracts. We identified the class II deacetylase HDAC5 as a novel promoting factor for expansions, joining the class I deacetylase HDAC3 that was previously identified. Double knockdowns were consistent with the possibility that MutSβ, HDAC3 and HDAC5 act through a common pathway to promote expansions of threshold-length TNRs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.