ArticlePLoS genetics2015
Heterozygosity for a hypomorphic Polβ mutation reduces the expansion frequency in a mouse model of the Fragile X-related disorders.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 45 citations in OpenAlex.
- DNA polymerase β suppresses somatic indels at CpG dinucleotides in developing cortical neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Repeat expansion in a fragile X model is independent of double strand break repair mediated by Pol θ, RAD52, RAD54 or RAD54B.Scientific reports · 2025Article
- In vivo CRISPR-Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington's disease.Nature genetics · 2025Article
- Review
- Repeat expansion in a Fragile X model is independent of double strand break repair mediated by Pol θ, Rad52, Rad54l or Rad54b.bioRxiv : the preprint server for biology · 2024Article
- Mouse models to explore the biological and organismic role of DNA polymerase beta.Environmental and molecular mutagenesis · 2024Review
- Genetic modifiers of repeat expansion disorders.Emerging topics in life sciences · 2023Article
- Polβ/XRCC1 heterodimerization dictates DNA damage recognition and basal Polβ protein levels without interfering with mouse viability or fertility.DNA repair · 2023Article
- Mechanisms of theInternational journal of molecular sciences · 2022Review
- A Double-Pronged Sword: XJB-5-131 Is a Suppressor of Somatic Instability and Toxicity in Huntington's Disease.Journal of Huntington's disease · 2022Review
- Non-canonical DNA/RNA structures associated with the pathogenesis of Fragile X-associated tremor/ataxia syndrome and Fragile X syndrome.Frontiers in genetics · 2022Review
- (Dys)function Follows Form: Nucleic Acid Structure, Repeat Expansion, and Disease Pathology inInternational journal of molecular sciences · 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
- Trinucleotide repeat instability via DNA base excision repair.DNA repair · 2020Review
- A point mutation in the nuclease domain of MLH3 eliminates repeat expansions in a mouse stem cell model of the Fragile X-related disorders.Nucleic acids research · 2020Article
- On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability.The Journal of biological chemistry · 2020Review
- Human MutLγ, the MLH1-MLH3 heterodimer, is an endonuclease that promotes DNA expansion.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Isolation and Analysis of the CGG-Repeat Size in Male and Female Gametes from a Fragile X Mouse Model.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Repeat Instability in the Fragile X-Related Disorders: Lessons from a Mouse Model.Brain sciences · 2019Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The Fragile X-related disorders (FXDs) are members of the Repeat Expansion Diseases, a group of human genetic conditions resulting from expansion of a specific tandem repeat. The FXDs result from expansion of a CGG/CCG repeat tract in the 5' UTR of the FMR1 gene. While expansion in a FXD mouse model is known to require some mismatch repair (MMR) proteins, our previous work and work in mouse models of another Repeat Expansion Disease show that early events in the base excision repair (BER) pathway play a role in the expansion process. One model for repeat expansion proposes that a non-canonical MMR process makes use of the nicks generated early in BER to load the MMR machinery that then generates expansions. However, we show here that heterozygosity for a Y265C mutation in Polβ, a key polymerase in the BER pathway, is enough to significantly reduce both the number of expansions seen in paternal gametes and the extent of somatic expansion in some tissues of the FXD mouse. These data suggest that events in the BER pathway downstream of the generation of nicks are also important for repeat expansion. Somewhat surprisingly, while the number of expansions is smaller, the average size of the residual expansions is larger than that seen in WT animals. This may have interesting implications for the mechanism by which BER generates expansions.
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