ArticleNature2017
Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 153 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
153 citing papers in PubMed, 2 syntheses or guidelines pooled it, 361 citations in OpenAlex.
- Assessment of associations between inhaled formaldehyde and lymphohematopoietic cancer through the integration of epidemiological and toxicological evidence with biological plausibility.Toxicological sciences : an official journal of the Society of Toxicology · 2024Pooled it
- Formaldehyde and Brain Disorders: A Meta-Analysis and Bioinformatics Approach.Neurotoxicity research · 2021Pooled it
- Excess folate elevates formaldehyde genotoxicity in cell lines but not in mice or humans.EMBO molecular medicine · 2026Article
- Process-integrated engineered resting cells for biocatalytic production of rare natural sugars from sole methanol molecules.Nature communications · 2026Article
- Aldehyde Detoxification in Cancer: Metabolic Guardians of the Genome.Biomolecules · 2026Review
- Metabolic drivers of genome instability in cancer: mechanisms and therapeutic opportunities.Experimental hematology & oncology · 2026Review
- Metabolite-induced DNA damage drives stochastic stem cell loss and clonal hematopoiesis.Cell stem cell · 2026Article
- Alternative Pathway for Methyl Supply through the Coupling of SHMT1 and PEMT to Maintain Astrocytic Homeostasis in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sensight enables quantitative multivariate engineering of high-performance chemical imaging tools.Nature communications · 2026Article
- 1-Amino-but-3-enes scavenge formaldehyde and glyoxylic acid.Communications chemistry · 2026Article
- Prebiotic Roles of Formaldehyde as an Activating Agent and a Building Block in Solid-State Peptide Modification.ACS bio & med chem Au · 2025Article
- A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis.Science (New York, N.Y.) · 2025Article
- Causes and consequences of RNA:protein cross-links - lessons from chemotherapy.Emerging topics in life sciences · 2025Review
- Formaldehyde and its surrogates as a C1 platform for defossilised modern societies.Chemical Society reviews · 2025Review
- Formate Reduces Ischemic Injury in Female Hearts Lacking Alcohol Dehydrogenase 5.FASEB bioAdvances · 2025Article
- ALDH9A1 deficiency as a source of endogenous DNA damage that requires repair by the Fanconi anemia pathway.The Journal of cell biology · 2025Article
- Methylobacterium extorquens PA1 utilizes multiple strategies to maintain formaldehyde homeostasis during methylotrophic growth.PLoS genetics · 2025Article
- Bacterial Volatile Organic Compounds as Potential Caries and Periodontitis Disease Biomarkers.International journal of molecular sciences · 2025Article
- Pan‑cancer analysis of oncogene SFXN1 to identify its prognostic and immunological roles in lung adenocarcinoma.Oncology reports · 2025Article
- Genome-wide mapping and quantification of DNA damage induced by catechol estrogens using Click-Probe-Seq and LC-MSCommunications biology · 2025Article
93 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
Abstract
The folate-driven one-carbon (1C) cycle is a fundamental metabolic hub in cells that enables the synthesis of nucleotides and amino acids and epigenetic modifications. This cycle might also release formaldehyde, a potent protein and DNA crosslinking agent that organisms produce in substantial quantities. Here we show that supplementation with tetrahydrofolate, the essential cofactor of this cycle, and other oxidation-prone folate derivatives kills human, mouse and chicken cells that cannot detoxify formaldehyde or that lack DNA crosslink repair. Notably, formaldehyde is generated from oxidative decomposition of the folate backbone. Furthermore, we find that formaldehyde detoxification in human cells generates formate, and thereby promotes nucleotide synthesis. This supply of 1C units is sufficient to sustain the growth of cells that are unable to use serine, which is the predominant source of 1C units. These findings identify an unexpected source of formaldehyde and, more generally, indicate that the detoxification of this ubiquitous endogenous genotoxin creates a benign 1C unit that can sustain essential metabolism.
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Identifiers
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.