ArticleAmerican journal of human genetics2003
Replication inhibitors modulate instability of an expanded trinucleotide repeat at the myotonic dystrophy type 1 disease locus in human cells.
Article in American journal of human genetics, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 85 citations in OpenAlex.
- Gene-Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability.Biomedicines · 2023Review
- Molecular Therapies for Myotonic Dystrophy Type 1: From Small Drugs to Gene Editing.International journal of molecular sciences · 2022Review
- 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
- Mitigating RNA Toxicity in Myotonic Dystrophy using Small Molecules.International journal of molecular sciences · 2019Review
- Myotonic dystrophy type 1 patient-derived iPSCs for the investigation of CTG repeat instability.Scientific reports · 2017Article
- Contracting CAG/CTG repeats using the CRISPR-Cas9 nickase.Nature communications · 2016Article
- FANCJ is essential to maintain microsatellite structure genome-wide during replication stress.Nucleic acids research · 2016Article
- Absence of MutSβ leads to the formation of slipped-DNA for CTG/CAG contractions at primate replication forks.DNA repair · 2016Article
- Semi-automated quantification of C9orf72 expansion size reveals inverse correlation between hexanucleotide repeat number and disease duration in frontotemporal degeneration.Acta neuropathologica · 2015Article
- Elevated Muscle-Specific miRNAs in Serum of Myotonic Dystrophy Patients Relate to Muscle Disease Progress.PloS one · 2015Article
- Disease-associated CAG·CTG triplet repeats expand rapidly in non-dividing mouse cells, but cell cycle arrest is insufficient to drive expansion.Nucleic acids research · 2014Article
- Length-dependent CTG·CAG triplet-repeat expansion in myotonic dystrophy patient-derived induced pluripotent stem cells.Human molecular genetics · 2013Article
- Inhibition of DNA synthesis facilitates expansion of low-complexity repeats: is strand slippage stimulated by transient local depletion of specific dNTPs?BioEssays : news and reviews in molecular, cellular and developmental biology · 2013Article
- Molecular genetics and genetic testing in myotonic dystrophy type 1.BioMed research international · 2013Review
- MSH3 polymorphisms and protein levels affect CAG repeat instability in Huntington's disease mice.PLoS genetics · 2013Article
- Altered replication in human cells promotes DMPK (CTG)(n) · (CAG)(n) repeat instability.Molecular and cellular biology · 2012Article
- DNA mismatch repair system: repercussions in cellular homeostasis and relationship with aging.Oxidative medicine and cellular longevity · 2012Review
- Review
- Topoisomerase 1 and single-strand break repair modulate transcription-induced CAG repeat contraction in human cells.Molecular and cellular biology · 2011Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene-specific CTG/CAG repeat expansion is associated with at least 14 human diseases, including myotonic dystrophy type 1 (DM1). Most of our understanding of trinucleotide instability is from nonhuman models, which have presented mixed results, supporting replication errors or processes independent of cell division as causes. Nevertheless, the mechanism occurring at the disease loci in patient cells is poorly understood. Using primary fibroblasts derived from a fetus with DM1, we have shown that spontaneous expansion of the diseased (CTG)(216) allele occurred in proliferating cells but not in quiescent cells. Expansions were "synchronous," with mutation frequencies approaching 100%. Furthermore, cells were treated with agents known to alter DNA synthesis but not to directly damage DNA. Inhibiting replication initiation with mimosine had no effect upon instability. Inhibiting both leading- and lagging-strand synthesis with aphidicolin or blocking only lagging strand synthesis with emetine significantly enhanced CTG expansions. It was striking that only the expanded DM1 allele was altered, leaving the normal allele, (CTG)(12), and other repeat loci unaffected. Standard and small-pool polymerase chain reaction revealed that inhibitors enhanced the magnitude of short expansions in most cells threefold, whereas 11%-25% of cells experienced gains of 122-170 repeats, to sizes of (CTG)(338)-(CTG)(386). Similar results were observed for an adult DM1 cell line. Our results support a role for the perturbation of replication fork dynamics in DM1 CTG expansions within patient fibroblasts. This is the first report that repeat-length alterations specific to a disease allele can be modulated by exogenously added compounds.
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