ArticleCell2017
A Class of Environmental and Endogenous Toxins Induces BRCA2 Haploinsufficiency and Genome Instability.
Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 3 of them syntheses that pooled it.
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
101 citing papers in PubMed, 3 syntheses or guidelines pooled it, 217 citations in OpenAlex.
- Cross-ancestry genome-wide association studies of liver function biomarkers uncover pleiotropic variants, systemic disease links and therapeutic targets.Genome medicine · 2026Pooled it
- Relationship between esophageal squamous cell carcinoma risk and alcohol-related ALDH2 and ADH1B polymorphisms: Evidence from a meta-analysis and Mendelian randomization analysis.Cancer medicine · 2023Pooled it
- Potential Adverse Public Health Effects Afforded by the Ingestion of Dietary Lipid Oxidation Product Toxins: Significance of Fried Food Sources.Nutrients · 2020Pooled it
- Aldehyde Detoxification in Cancer: Metabolic Guardians of the Genome.Biomolecules · 2026Review
- Endogenous and environmental factors that induce DNA replication defects and genomic instability in ER-negative heterozygous BRCA1 cells.Scientific reports · 2026Article
- Review
- Long-term exposure to the ethanol-derived metabolite acetaldehyde elevates structural genomic alterations but not base substitutions.Communications biology · 2026Article
- R‑loops in hepatocellular carcinoma: Bridging genomic instability and therapeutic opportunity (Review).Molecular medicine reports · 2026Review
- A recurrent pathogenic BRCA2 truncating variant reveals a role for BRCA2-PCAF complex in modulating NF-κB-driven transcription.Nature communications · 2025Article
- HSP90 buffers deleterious genetic variations in BRCA1.Molecular cell · 2025Article
- BRCA2 deficiency and replication stress drive APOBEC3-Mediated genomic instability.Nature communications · 2025Article
- DSS1 is required for proper Integrator-PP2A function.Nature communications · 2025Article
- Curcumin Induces Homologous Recombination Deficiency by BRCA2 Degradation in Breast Cancer and Normal Cells.Cancers · 2025Article
- BRCA1 and BRCA2: from cancer susceptibility to synthetic lethality.Genes & development · 2025Review
- From mechanisms of carcinogenesis to early intervention: an interview with Ashok Venkitaraman.Disease models & mechanisms · 2024Article
- Sodium arsenite-induced DNA methylation alterations exacerbated by p53 knockout in MCF7 cells.Heliyon · 2024Article
- The methionine cycle and its cancer implications.Oncogene · 2024Review
- Formaldehyde initiates memory and motor impairments under weightlessness condition.NPJ microgravity · 2024Review
- R-loops' m6A modification and its roles in cancers.Molecular cancer · 2024Review
- Exogenous and endogenous formaldehyde-induced DNA damage in the aging brain: mechanisms and implications for brain diseases.Cell biology and toxicology · 2024Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Mutations truncating a single copy of the tumor suppressor, BRCA2, cause cancer susceptibility. In cells bearing such heterozygous mutations, we find that a cellular metabolite and ubiquitous environmental toxin, formaldehyde, stalls and destabilizes DNA replication forks, engendering structural chromosomal aberrations. Formaldehyde selectively depletes BRCA2 via proteasomal degradation, a mechanism of toxicity that affects very few additional cellular proteins. Heterozygous BRCA2 truncations, by lowering pre-existing BRCA2 expression, sensitize to BRCA2 haploinsufficiency induced by transient exposure to natural concentrations of formaldehyde. Acetaldehyde, an alcohol catabolite detoxified by ALDH2, precipitates similar effects. Ribonuclease H1 ameliorates replication fork instability and chromosomal aberrations provoked by aldehyde-induced BRCA2 haploinsufficiency, suggesting that BRCA2 inactivation triggers spontaneous mutagenesis during DNA replication via aberrant RNA-DNA hybrids (R-loops). These findings suggest a model wherein carcinogenesis in BRCA2 mutation carriers can be incited by compounds found pervasively in the environment and generated endogenously in certain tissues with implications for public health.
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What OpenQuestion holds
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.