ArticleProceedings of the National Academy of Sciences of the United States of America2009
Zinc-finger directed double-strand breaks within CAG repeat tracts promote repeat instability in human cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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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.
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Who cites it
53 citing papers in PubMed, 92 citations in OpenAlex.
- CRISPR-based gene therapy for huntington's disease: current advances and future prospects.Neurogenetics · 2025Review
- Review
- Muscle-specific gene editing improves molecular and phenotypic defects in a mouse model of myotonic dystrophy type 1.Clinical and translational medicine · 2025Article
- CRISPR/Cas9-induced double-strand breaks in the huntingtin locus lead to CAG repeat contraction through DNA end resection and homology-mediated repair.BMC biology · 2024Article
- Advancing diabetes management: Exploring pancreatic beta-cell restoration's potential and challenges.World journal of gastroenterology · 2024Review
- Cas9 nickase-mediated contractions of CAG/CTG repeats are transcription-dependent and replication-independent.NAR molecular medicine · 2024Article
- Latest advances on new promising molecular-based therapeutic approaches for Huntington's disease.Journal of translational internal medicine · 2024Article
- Association between dietary zinc intake and epilepsy: findings from NHANES 2013-2018 and a Mendelian randomization study.Frontiers in nutrition · 2024Article
- CRISPR-Based Genome-Editing Tools for Huntington's Disease Research and Therapy.Neuroscience bulletin · 2022Review
- Molecular Therapies for Myotonic Dystrophy Type 1: From Small Drugs to Gene Editing.International journal of molecular sciences · 2022Review
- Review
- Genome engineering and disease modelingWorld journal of stem cells · 2021Review
- Article
- Huntington's Disease: New Frontiers in Therapeutics.Current neurology and neuroscience reports · 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
- Application of CRISPR-Cas9-Mediated Genome Editing for the Treatment of Myotonic Dystrophy Type 1.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Therapeutic Update on Huntington's Disease: Symptomatic Treatments and Emerging Disease-Modifying Therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Review
- On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability.The Journal of biological chemistry · 2020Review
- A slipped-CAG DNA-binding small molecule induces trinucleotide-repeat contractions in vivo.Nature genetics · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Expanded triplet repeats have been identified as the genetic basis for a growing number of neurological and skeletal disorders. To examine the contribution of double-strand break repair to CAG x CTG repeat instability in mammalian systems, we developed zinc finger nucleases (ZFNs) that recognize and cleave CAG repeat sequences. Engineered ZFNs use a tandem array of zinc fingers, fused to the FokI DNA cleavage domain, to direct double-strand breaks (DSBs) in a site-specific manner. We first determined that the ZFNs cleave CAG repeats in vitro. Then, using our previously described tissue culture assay for identifying modifiers of CAG repeat instability, we found that transfection of ZFN-expression vectors induced up to a 15-fold increase in changes to the CAG repeat in human and rodent cell lines, and that longer repeats were much more sensitive to cleavage than shorter ones. Analysis of individual colonies arising after treatment revealed a spectrum of events consistent with ZFN-induced DSBs and dominated by repeat contractions. We also found that expressing a dominant-negative form of RAD51 in combination with a ZFN, dramatically reduced the effect of the nuclease, suggesting that DSB-induced repeat instability is mediated, in part, through homology directed repair. These studies identify a ZFN as a useful reagent for characterizing the effects of DSBs on CAG repeats in cells.
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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.