ArticleCell reports2016
Stalled DNA Replication Forks at the Endogenous GAA Repeats Drive Repeat Expansion in Friedreich's Ataxia Cells.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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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
47 citing papers in PubMed, 67 citations in OpenAlex.
- Edited HSPCs rescue frataxin deficiency and inflammation-driven multisystemic pathology in Friedreich's ataxia mice.The Journal of clinical investigation · 2026Article
- RNAs anchoring replication complex control initiation and firing of DNA replication.Nature communications · 2026Article
- Human pluripotent stem cell models of Friedreich's ataxia: innovations, considerations, and future perspectives.Stem cell research & therapy · 2026Review
- Overcoming natural replication barriers formed by DNA structures and the role of repositioning to the nuclear periphery.DNA repair · 2025Review
- Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025Review
- The Influence of CG sites on dynamic DNA sequence mutagenesis in the genomic evolution of mammalian lifespan.Nucleic acids research · 2025Article
- The origin of mirror repeats in the human genome.Nucleic acids research · 2025Article
- 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
- Stabilization of expandable DNA repeats by the replication factor Mcm10 promotes cell viability.Nature communications · 2024Article
- Review
- Triplex H-DNA structure: the long and winding road from the discovery to its role in human disease.NAR molecular medicine · 2024Article
- Review
- Patient-derived iPSC models of Friedreich ataxia: a new frontier for understanding disease mechanisms and therapeutic application.Translational neurodegeneration · 2023Review
- Large-scale expansions of Friedreich's ataxia GAA•TTC repeats in an experimental human system: role of DNA replication and prevention by LNA-DNA oligonucleotides and PNA oligomers.Nucleic acids research · 2023Article
- S1-END-seq reveals DNA secondary structures in human cells.Molecular cell · 2022Article
- Review
- Creation and resolution of non-B-DNA structural impediments during replication.Critical reviews in biochemistry and molecular biology · 2022Article
- The mechanism of replication stalling and recovery within repetitive DNA.Nature communications · 2022Article
- Recessive cerebellar and afferent ataxias - clinical challenges and future directions.Nature reviews. Neurology · 2022Review
- Group II intron and repeat-rich red algal mitochondrial genomes demonstrate the dynamic recent history of autocatalytic RNAs.BMC biology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Friedreich's ataxia (FRDA) is caused by the expansion of GAA repeats located in the Frataxin (FXN) gene. The GAA repeats continue to expand in FRDA patients, aggravating symptoms and contributing to disease progression. The mechanism leading to repeat expansion and decreased FXN transcription remains unclear. Using single-molecule analysis of replicated DNA, we detected that expanded GAA repeats present a substantial obstacle for the replication machinery at the FXN locus in FRDA cells. Furthermore, aberrant origin activation and lack of a proper stress response to rescue the stalled forks in FRDA cells cause an increase in 3'-5' progressing forks, which could enhance repeat expansion and hinder FXN transcription by head-on collision with RNA polymerases. Treatment of FRDA cells with GAA-specific polyamides rescues DNA replication fork stalling and alleviates expansion of the GAA repeats, implicating DNA triplexes as a replication impediment and suggesting that fork stalling might be a therapeutic target for FRDA.
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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.