ArticleNucleic acids research2017
MutSβ abundance and Msh3 ATP hydrolysis activity are important drivers of CTG•CAG repeat expansions.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- Targeted quantification assays for DNA repair and handling proteins and interactions in Huntington's disease models.bioRxiv : the preprint server for biology · 2026Article
- Double strand breaks drive toxicity in a Huntington's disease mouse model with or without somatic expansion.Nature communications · 2026Article
- Genetic or pharmacological disruption of the MSH3 Y245/K246 IDL binding pocket slows CAG repeat expansion.NAR molecular medicine · 2026Article
- Mismatch repair MLH complexes make distinct contributions to post-replicative mismatch repair versus trinucleotide repeat expansions.bioRxiv : the preprint server for biology · 2026Article
- Huntington disease: somatic expansion, pathobiology and therapeutics.Nature reviews. Neurology · 2026Review
- Disruption of protein-protein interaction hotspots in the C-terminal domain of MLH1 confers mismatch repair deficiency.NAR cancer · 2025Article
- RNA/DNA-binding protein TDP43 regulates DNA mismatch repair genes with implications for genome stability.Nucleic acids research · 2025Article
- RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability.bioRxiv : the preprint server for biology · 2025Article
- Double strand breaks drive toxicity in Huntington's disease mice with or without somatic expansion.bioRxiv : the preprint server for biology · 2025Article
- Mechanism of circRNA_4083 Circularization and Its Role in Regulating Cell Viability.Animals : an open access journal from MDPI · 2025Article
- Msh2-Msh3 DNA-binding is not sufficient to promote trinucleotide repeat expansions in Saccharomyces cerevisiae.Genetics · 2025Article
- Review
- Therapeutic validation of MMR-associated genetic modifiers in a human ex vivo model of Huntington disease.American journal of human genetics · 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
- MutSβ protects common fragile sites by facilitating homology-directed repair at DNA double-strand breaks with secondary structures.Nucleic acids research · 2024Article
- Genetic modifiers of repeat expansion disorders.Emerging topics in life sciences · 2023Article
- Tandem MutSβ binding to long extruded DNA trinucleotide repeats underpins pathogenic expansions.bioRxiv : the preprint server for biology · 2023Article
- Elevated MSH2 MSH3 expression interferes with DNA metabolism in vivo.Nucleic acids research · 2023Article
- Can MSH3 lowering stop HTT repeat expansion in its CAG tract?Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
CTG•CAG repeat expansions cause at least twelve inherited neurological diseases. Expansions require the presence, not the absence, of the mismatch repair protein MutSβ (Msh2-Msh3 heterodimer). To evaluate properties of MutSβ that drive expansions, previous studies have tested under-expression, ATPase function or polymorphic variants of Msh2 and Msh3, but in disparate experimental systems. Additionally, some variants destabilize MutSβ, potentially masking the effects of biochemical alterations of the variations. Here, human Msh3 was mutated to selectively inactivate MutSβ. Msh3-/- cells are severely defective for CTG•CAG repeat expansions but show full activity on contractions. Msh3-/- cells provide a single, isogenic system to add back Msh3 and test key biochemical features of MutSβ on expansions. Msh3 overexpression led to high expansion activity and elevated levels of MutSβ complex, indicating that MutSβ abundance drives expansions. An ATPase-defective Msh3 expressed at normal levels was as defective in expansions as Msh3-/- cells, indicating that Msh3 ATPase function is critical for expansions. Expression of two Msh3 polymorphic variants at normal levels showed no detectable change in expansions, suggesting these polymorphisms primarily affect Msh3 protein stability, not activity. In summary, CTG•CAG expansions are limited by the abundance of MutSβ and rely heavily on Msh3 ATPase function.
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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.