ArticleNucleic acids research2004
Replication-mediated instability of the GAA triplet repeat mutation in Friedreich ataxia.
Article in Nucleic acids research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Unrecognized high prevalence of expanded composite repeats in Friedreich ataxia.Human molecular genetics · 2026Article
- Base editing of trinucleotide repeats that cause Huntington's disease and Friedreich's ataxia reduces somatic repeat expansions in patient cells and in mice.Nature genetics · 2025Article
- Triplex H-DNA structure: the long and winding road from the discovery to its role in human disease.NAR molecular medicine · 2024Article
- Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.Nature reviews. Genetics · 2024Review
- The Regulation of the Disease-Causing GeneCells · 2024Review
- Pathogenic CANVAS (AAGGG)n repeats stall DNA replication due to the formation of alternative DNA structures.Nucleic acids research · 2024Article
- 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
- Review
- Non-canonical DNA structures: Diversity and disease association.Frontiers in genetics · 2022Review
- On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability.The Journal of biological chemistry · 2020Review
- Defects in the GINS complex increase the instability of repetitive sequences via a recombination-dependent mechanism.PLoS genetics · 2019Article
- Paradigm for disease deconvolution in rare neurodegenerative disorders in Indian population: insights from studies in cerebellar ataxias.Journal of genetics · 2018Article
- Distinct Mechanisms of Nuclease-Directed DNA-Structure-Induced Genetic Instability in Cancer Genomes.Cell reports · 2018Article
- Large Interruptions of GAA Repeat Expansion Mutations in Friedreich Ataxia Are Very Rare.Frontiers in cellular neuroscience · 2018Article
- Viral delivery ofDisease models & mechanisms · 2017Article
- Article
- New Perspectives on DNA and RNA Triplexes As Effectors of Biological Activity.PLoS genetics · 2015Review
- Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA·TTC) associated with Friedreich's ataxia.DNA repair · 2013Article
- Genome-wide screen identifies pathways that govern GAA/TTC repeat fragility and expansions in dividing and nondividing yeast cells.Molecular cell · 2012Article
- Effects of Friedreich's ataxia GAA repeats on DNA replication in mammalian cells.Nucleic acids research · 2012Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Friedreich ataxia is caused by the expansion of a polymorphic and unstable GAA triplet repeat in the FRDA gene, but the mechanisms for its instability are poorly understood. Replication of (GAA*TTC)n sequences (9-105 triplets) in plasmids propagated in Escherichia coli displayed length- and orientation-dependent instability. There were small length variations upon replication in both orientations, but large contractions were frequently observed when GAA was the lagging strand template. DNA replication was also significantly slower in this orientation. To evaluate the physiological relevance of our findings, we analyzed peripheral leukocytes from human subjects carrying repeats of similar length (8-107 triplets). Analysis of 9400 somatic FRDA molecules using small-pool PCR revealed a similar mutational spectrum, including large contractions. The threshold length for the initiation of somatic instability in vivo was between 40 and 44 triplets, corresponding to the length of a eukaryotic Okazaki fragment. Consistent with the stabilization of premutation alleles during germline transmission, we also found that instability of somatic cells in vivo and repeats propagated in E.coli were abrogated by (GAGGAA)n hexanucleotide interruptions. Our data demonstrate that the GAA triplet repeat mutation in Friedreich ataxia is destabilized, frequently undergoing large contractions, during DNA replication.
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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.