ArticlePloS one2014
MutLα heterodimers modify the molecular phenotype of Friedreich ataxia.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 25 citations in OpenAlex.
- The origin of mirror repeats in the human genome.Nucleic acids research · 2025Article
- Triplex H-DNA structure: the long and winding road from the discovery to its role in human disease.NAR molecular medicine · 2024Article
- Somatic and intergenerational G4C2 hexanucleotide repeat instability in a human C9orf72 knock-in mouse model.Nucleic acids research · 2024Article
- Therapeutic validation of MMR-associated genetic modifiers in a human ex vivo model of Huntington disease.American journal of human genetics · 2024Article
- Genetic modifiers of repeat expansion disorders.Emerging topics in life sciences · 2023Article
- Review
- 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
- 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
- The Contribution of Somatic Expansion of the CAG Repeat to Symptomatic Development in Huntington's Disease: A Historical Perspective.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
- A Variation in FGF14 Is Associated with Downbeat Nystagmus in a Genome-Wide Association Study.Cerebellum (London, England) · 2020Article
- On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability.The Journal of biological chemistry · 2020Review
- Large-scale contractions of Friedreich's ataxia GAA repeats in yeast occur during DNA replication due to their triplex-forming ability.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Review
- DNA mismatch repair in trinucleotide repeat instability.Science China. Life sciences · 2017Review
- Close encounters: Moving along bumps, breaks, and bubbles on expanded trinucleotide tracts.DNA repair · 2017Review
- Genetic Contributors to Intergenerational CAG Repeat Instability in Huntington's Disease Knock-In Mice.Genetics · 2017Article
- Crosstalk between MSH2-MSH3 and polβ promotes trinucleotide repeat expansion during base excision repair.Nature communications · 2016Article
- The Repeat Expansion Diseases: The dark side of DNA repair.DNA repair · 2015Review
- Friedreich ataxia: failure of GABA-ergic and glycinergic synaptic transmission in the dentate nucleus.Journal of neuropathology and experimental neurology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundFriedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. METHODOLOGY/PRINCIPAL
findingsTo determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. CONCLUSIONS/SIGNIFICANCE: Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.