ArticleProceedings of the National Academy of Sciences of the United States of America2015
Environmental stress induces trinucleotide repeat mutagenesis in human cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Atrazine Induces Reproductive Toxicity in anBiomedicines · 2025Article
- Transposon activity and nucleotide triplet instability: new perspectives on their potential interplay in brain disorders.Frontiers in neuroscience · 2025Article
- The Role of NRF2 in Trinucleotide Repeat Expansion Disorders.Antioxidants (Basel, Switzerland) · 2024Review
- Redox dysregulation as a driver for DNA damage and its relationship to neurodegenerative diseases.Translational neurodegeneration · 2023Review
- Gene-Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability.Biomedicines · 2023Review
- Roles of DNA damage in renal tubular epithelial cells injury.Frontiers in physiology · 2023Review
- Suppression of trinucleotide repeat expansion in spermatogenic cells in Huntington's disease.Journal of assisted reproduction and genetics · 2022Article
- CDT1 facilitates metastasis in prostate cancer and correlates with cell cycle regulation.Cancer biomarkers : section A of Disease markers · 2022Article
- Mutation-selection balance and compensatory mechanisms in tumour evolution.Nature reviews. Genetics · 2021Review
- TCF4-mediated Fuchs endothelial corneal dystrophy: Insights into a common trinucleotide repeat-associated disease.Progress in retinal and eye research · 2021Review
- Fuchs endothelial corneal dystrophy: The vicious cycle of Fuchs pathogenesis.Progress in retinal and eye research · 2021Review
- Modifiers of CAG/CTG Repeat Instability: Insights from Mammalian Models.Journal of Huntington's disease · 2021Review
- Nickel Carcinogenesis Mechanism: DNA Damage.International journal of molecular sciences · 2019Review
- Article
- Environmental stresses induce karyotypic instability in colorectal cancer cells.Molecular biology of the cell · 2019Article
- Trinucleotide Repeat Expansion Diseases, RNAi, and Cancer.Trends in cancer · 2018Review
- Mechanisms of genetic instability caused by (CGG)Nature structural & molecular biology · 2018Article
- Tandem repeats mediating genetic plasticity in health and disease.Nature reviews. Genetics · 2018Review
- Of Men and Mice: Modeling the Fragile X Syndrome.Frontiers in molecular neuroscience · 2018Article
- Rapid Generation of Multiple Loci-Engineered Marker-free Poxvirus and Characterization of a Clinical-Grade Oncolytic Vaccinia Virus.Molecular therapy. Methods & clinical development · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)-the cause of multiple human diseases-have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential.
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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.