Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism
Open accessAbstract
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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Two mito-1C metabolism genes, SHMT2 and MTHFD1L, and ESD were identified in the CRISPRko screen.
“Notably, two mito-1C metabolism genes, SHMT2 and MTHFD1L, and the S-formylglutathione hydrolase gene, ESD, involved in GSH-mediated formaldehyde detoxification (12) were identified in the CRISPRko screen.”
From Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction (2022) · cites this paper as [12]
The section ‘ADH5 fuels the growth of 1C-cycle-deficient cells’ describes S-formylglutathione hydrolase regenerating GSH as part of a formaldehyde-detoxification route. It does not identify that hydrolase as ESD. The citation is attached to the detoxification clause; this source does not report the claimed identification of SHMT2, MTHFD1L and ESD in a CRISPR knockout screen. (LLM, conf=0.83)
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Cites
Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity
Ran, F. A., Hsu, P. D., Lin, C.-Y., Gootenberg, J. S., Konermann, S., Trevino, A. E., Scott, D. A., Inoue, A., Matoba, S., Zhang, Y., et al. (2013) · Cell · doi:10.1016/j.cell.2013.08.021 · Cited by 3,299 · see citing works
One-Carbon Metabolism in Health and Disease
Ducker, G. S., & Rabinowitz, J. D. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.009 · Cited by 2,239 · see citing works
Farber, S., Diamond, L. K., Mercer, R. D., Sylvester, R. F., & Wolff, J. A. (1948) · New England Journal of Medicine · doi:10.1056/nejm194806032382301 · Cited by 1,806 · see citing works
Compartmentalization of Mammalian Folate-Mediated One-Carbon Metabolism
Tibbetts, A. S., & Appling, D. R. (2010) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.012809.104810 · Cited by 692 · see citing works
Reversal of cytosolic one-carbon flux compensates for loss of the mitochondrial folate pathway
Ducker, G. S., Chen, L., Morscher, R. J., Ghergurovich, J. M., Esposito, M., Teng, X., Kang, Y., & Rabinowitz, J. D. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.016 · Cited by 419 · see citing works
Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function
Garaycoechea, J. I., Crossan, G. P., Langevin, F., Daly, M. G., Arends, M. J., & Patel, K. J. (2012) · Nature · doi:10.1038/nature11368 · Cited by 386 · see citing works
Self-citationEndogenous Formaldehyde Is a Hematopoietic Stem Cell Genotoxin and Metabolic Carcinogen
Pontel, L. B., Rosado, I. V., Burgos-Barragan, G., Garaycoechea, J. I., Yu, R., Arends, M. J., Chandrasekaran, G., Broecker, V., Wei, W., Liu, L., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.08.020 · Cited by 384 · see citing works
Self-citationAn Aza-Cope Reactivity-Based Fluorescent Probe for Imaging Formaldehyde in Living Cells
Brewer, T. F., & Chang, C. J. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b05340 · Cited by 271 · see citing works
Self-citationHeck, H. D., Casanova, M., DODD, P. B., Schachter, E. N., Witek, T. J., & Tosun, T. (1985) · American Industrial Hygiene Association Journal · doi:10.1080/15298668591394275 · Cited by 248 · see citing works
Formaldehyde Dehydrogenase from Human Liver
Uotila, L., & Koivusalo, M. (1974) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)81287-5 · Cited by 216 · see citing works
Mutant loxP vectors for selectable marker recycle and conditional knock-outs
Arakawa, H., Lodygin, D., & Buerstedde, J.-M. (2001) · BMC Biotechnology · doi:10.1186/1472-6750-1-7 · Cited by 199 · see citing works
Mechanisms of human histone and nucleic acid demethylases
Walport, L. J., Hopkinson, R. J., & Schofield, C. J. (2012) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2012.09.015 · Cited by 195 · see citing works
Formaldehyde catabolism is essential in cells deficient for the Fanconi anemia DNA-repair pathway
Rosado, I. V., Langevin, F., Crossan, G. P., Takata, M., & Patel, K. J. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2173 · Cited by 184 · see citing works
Self-citationSerine one-carbon catabolism with formate overflow
Meiser, J., Tumanov, S., Maddocks, O., Labuschagne, C. F., Athineos, D., Van Den Broek, N., Mackay, G. M., Gottlieb, E., Blyth, K., Vousden, K., et al. (2016) · Science Advances · doi:10.1126/sciadv.1601273 · Cited by 174 · see citing works
Self-citationLuo, W., Li, H., Zhang, Y., & ANG, C. Y. W. (2001) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(00)00552-1 · Cited by 149 · see citing works
Bruemmer, K. J., Walvoord, R. R., Brewer, T. F., Burgos-Barragan, G., Wit, N., Pontel, L. B., Patel, K. J., & Chang, C. J. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.6b12460 · Cited by 140 · see citing works
Self-citationThe Structure of “Active Formaldehyde” (N5, N10 -Methylene Tetrahydrofolic Acid)1
Osborn, M., Talbert, P. T., & Huennekens, F. M. (1960) · Journal of the American Chemical Society · doi:10.1021/ja01503a043 · Cited by 120 · see citing works
Brouwer, V. D., Zhang, G., Storozhenko, S., Straeten, D. V. D., & Lambert, W. E. (2007) · Phytochemical Analysis · doi:10.1002/pca.1006 · Cited by 115 · see citing works
High intake of folic acid disrupts embryonic development in mice
Pickell, L., Brown, K., Li, D., Wang, X., Deng, L.-Y., Wu, Q. H., Selhub, J., Luo, L., Jerome‐Majewska, L. A., & Rozen, R. R. (2010) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.20754 · Cited by 111 · see citing works
Purification and Properties of S-Formylglutathione Hydrolase from Human Liver
Uotila, L., & Koivusalo, M. (1974) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)81288-7 · Cited by 100 · see citing works
Folic acid supplementation can adversely affect murine neural tube closure and embryonic survival
Marean, A., Graf, A. E., Zhang, Y., & Niswander, L. A. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr289 · Cited by 89 · see citing works
McCarthy, E. A., Titus, S. A., Taylor, S. M., Jackson‐Cook, C. K., & Moran, R. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403677200 · Cited by 68 · see citing works
Patel, H., Pietro, E. D., & MacKenzie, R. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301718200 · Cited by 62 · see citing works
Oxidative degradation of dihydrofolate and tetrahydrofolate
Chippel, D., & Scrimgeour, K. G. (1970) · Canadian Journal of Biochemistry · doi:10.1139/o70-156 · Cited by 55 · see citing works
Impact of dietary folic acid on reduced folates in mouse plasma and tissues
Schmitz, J. C., Grlndey, G. B., Schultz, R. M., & Priest, D. G. (1994) · Biochemical Pharmacology · doi:10.1016/0006-2952(94)90103-1 · Cited by 50 · see citing works
Chen, Z., Rozen, R. R., Ghandour, H., & Selhub, J. (2004) · Journal of Nutrition · doi:10.1093/jn/134.11.2975 · Cited by 49 · see citing works
Atmospheric pressure chemical ionization mass spectrometry of aldehydes in biological matrices
Nagy, K., Pollreisz, F., Takáts, Z., & Vékey, K. (2004) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.1648 · Cited by 48 · see citing works
Wit, N., Buoninfante, O. A., van den Berk, P. C. M., Jansen, J. G., Hogenbirk, M. A., de Wind, N., & Jacobs, H. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1301 · Cited by 45 · see citing works
Self-citationLawrence, S. A., Titus, S. A., Ferguson, J., Heineman, A., Taylor, S. M., & Moran, R. G. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.593244 · Cited by 40 · see citing works
Urinary Excretion of Deuterium-Labeled Folate and the Metabolite p-Aminobenzoylglutamate in Humans
Kownacki-Brown, P. A., Wang, C., Bailey, L. B., Toth, J. P., & Gregory, J. F. (1993) · Journal of Nutrition · doi:10.1093/jn/123.6.1101 · Cited by 32 · see citing works
Human Mus81 and FANCB independently contribute to repair of DNA damage during replication
Nomura, Y., Adachi, N., & Koyama, H. (2007) · Genes to Cells · doi:10.1111/j.1365-2443.2007.01124.x · Cited by 28 · see citing works
Witham, K. L., Butcher, N. J., Sugamori, K. S., Brenneman, D., Grant, D. M., & Minchin, R. F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077923 · Cited by 22 · see citing works
Murphy, M., & Scott, J. M. (1979) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(79)90071-0 · Cited by 22 · see citing works
The fate of [3H]folic acid in folate-adequate rats
Scott, K. C., & Gregory, J. F. (1996) · The Journal of Nutritional Biochemistry · doi:10.1016/0955-2863(96)00026-5 · Cited by 17 · see citing works
Horne, D. W. (2003) · Journal of Nutrition · doi:10.1093/jn/133.2.476 · Cited by 15 · see citing works
Alcohol Dehydrogenase 5 Is a Source of Formate for De Novo Purine Biosynthesis in HepG2 Cells
Bae, S., Chon, J., Field, M. S., & Stover, P. J. (2017) · Journal of Nutrition · doi:10.3945/jn.116.244467 · Cited by 14 · see citing works
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Redox Signaling by Reactive Electrophiles and Oxidants
Parvez, S., Long, M. J. C., Poganik, J. R., & Aye, Y. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00698 · Cited by 357 · see citing works
Activity‐Based Sensing: A Synthetic Methods Approach for Selective Molecular Imaging and Beyond
Bruemmer, K. J., Crossley, S. W. M., & Chang, C. J. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201909690 · Cited by 266 · see citing works
Self-citationShi, H., Ge, X., Ma, X., Zheng, M., Cui, X., Pan, W. X., Zheng, P., Yang, X., Zhang, P., Hu, M., et al. (2021) · Microbiome · doi:10.1186/s40168-021-01172-0 · Cited by 248 · see citing works
Toward a better understanding of folate metabolism in health and disease
Zheng, Y., & Cantley, L. C. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20181965 · Cited by 235 · see citing works
Metabolic regulation of chromatin modifications and gene expression
Schvartzman, J. M., Thompson, C. B., & Finley, L. W. S. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201803061 · Cited by 233 · see citing works
Formate metabolism in health and disease
Pietzke, M., Meiser, J., & Vazquez, A. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2019.05.012 · Cited by 218 · see citing works
Self-citationBruemmer, K. J., Green, O., Su, T. A., Shabat, D., & Chang, C. J. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201802143 · Cited by 200 · see citing works
Self-citationFormaldehyde metabolism and its impact on human health
Reingruber, H., & Pontel, L. B. (2018) · Current Opinion in Toxicology · doi:10.1016/j.cotox.2018.07.001 · Cited by 192 · see citing works
Self-citationDingler, F. A., Wang, M., Mu, A., Millington, C. L., Oberbeck, N., Watcham, S., Pontel, L. B., Kamimae-Lanning, A. N., Langevin, F., Nadler, C., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.10.012 · Cited by 185 · see citing works
Self-citationHow formaldehyde reacts with amino acids
Kamps, J. J. A. G., Hopkinson, R. J., Schofield, C. J., & Claridge, T. D. W. (2019) · Communications Chemistry · doi:10.1038/s42004-019-0224-2 · Cited by 177 · see citing works
Ohata, J., Bruemmer, K. J., & Chang, C. J. (2019) · Accounts of Chemical Research · doi:10.1021/acs.accounts.9b00386 · Cited by 135 · see citing works
Self-citationCancer Metabolism Drives a Stromal Regenerative Response
Schwörer, S., Vardhana, S. A., & Thompson, C. B. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.015 · Cited by 121 · see citing works
The complexity of the serine glycine one-carbon pathway in cancer
Reina‐Campos, M., Díaz-Meco, M. T., & Moscat, J. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201907022 · Cited by 123 · see citing works
Increased formate overflow is a hallmark of oxidative cancer
Meiser, J., Schuster, A. M., Pietzke, M., Voorde, J. V., Athineos, D., Oizel, K., Burgos-Barragan, G., Wit, N., Dhayade, S., Morton, J. P., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03777-w · Cited by 119 · see citing works
Self-citationUmansky, C., Morellato, A. E., Scheidegger, M., Rieckher, M., Martinefski, M., Fernández, G. A., Kolesnikova, K., Vesting, A. J., Karakasilioti, I., Reingruber, H., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28242-7 · Cited by 119 · see citing works
Self-citationNewman, A. C., Falcone, M., Uribe, A. H., Zhang, T., Athineos, D., Pietzke, M., Vázquez, A., Blyth, K., & Maddocks, O. D. K. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.03.019 · Cited by 111 · see citing works
Self-citationMitochondrial One-Carbon Pathway Supports Cytosolic Folate Integrity in Cancer Cells
Zheng, Y., Lin, T.-Y., Lee, G., Paddock, M. N., Momb, J., Cheng, Z., Li, Q., Fei, D. L., Stein, B. D., Ramsamooj, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.041 · Cited by 106 · see citing works
Fujihara, K. M., Zhang, B. Z., Jackson, T. D., Ogunkola, M. O., Nijagal, B., Milne, J. V., Sallman, D. A., Ang, C.-S., Nikolic, I., Kearney, C. J., et al. (2022) · Science Advances · doi:10.1126/sciadv.abm9427 · Cited by 103 · see citing works
Toh, J. D. W., Crossley, S. W. M., Bruemmer, K. J., Ge, E. J., He, D., Iovan, D. A., & Chang, C. J. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2007349117 · Cited by 102 · see citing works
Self-citationRauch, M., Strater, Z. M., & Parkin, G. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b08342 · Cited by 100 · see citing works
The toxic side of one-carbon metabolism and epigenetics
Morellato, A. E., Umansky, C., & Pontel, L. B. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101850 · Cited by 92 · see citing works
Self-citationDNA–Protein Crosslinks and Their Resolution
Weickert, P., & Stingele, J. (2022) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-105820 · Cited by 92 · see citing works
Ma, Y., Tang, Y., Zhao, Y., & Lin, W. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b02119 · Cited by 91 · see citing works
New directions of activity-based sensing for in vivo NIR imaging
East, A. K., Lucero, M. Y., & Chan, J. (2020) · Chemical Science · doi:10.1039/d0sc03096a · Cited by 91 · see citing works
Xu, H., Xu, H., Ma, S., Chen, X., Huang, L., Chen, J., Gao, F., Wang, R., Lou, K., & Wang, W. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b09794 · Cited by 89 · see citing works
Oka, Y., Hamada, M., Nakazawa, Y., Muramatsu, H., Okuno, Y., Higasa, K., Shimada, M., Takeshima, H., Hanada, K., Hirano, T., et al. (2020) · Science Advances · doi:10.1126/sciadv.abd7197 · Cited by 92 · see citing works
Formaldehyde regulates S -adenosylmethionine biosynthesis and one-carbon metabolism
Pham, V. N., Bruemmer, K. J., Toh, J. D. W., Ge, E. J., Tenney, L., Ward, C. C., Dingler, F. A., Millington, C. L., García-Prieto, C. A., Pulos-Holmes, M. C., et al. (2023) · Science · doi:10.1126/science.abp9201 · Cited by 88 · see citing works
Self-citationPeng, W., Yue, X., Chen, H., Ling, N., Zhou, Q., Yu, Q., Wei, Z., Guan, R., Lam, S. S., Rinklebe, J., et al. (2022) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2022.129304 · Cited by 86 · see citing works
Metabolic regulation of somatic stem cells in vivo
Meacham, C. E., DeVilbiss, A. W., & Morrison, S. J. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00462-1 · Cited by 85 · see citing works
Das, S., Indurthi, H. K., Asati, P., Saha, P., & Sharma, D. K. (2021) · Dyes and Pigments · doi:10.1016/j.dyepig.2021.110074 · Cited by 83 · see citing works
Surface oxygen chemistry of metal oxide semiconductors for gas-sensing applications
Li, J., Na, E., Liang, X., Liang, Q., Fan, M., Chen, H., Li, G., & Zou, X. (2024) · Inorganic Chemistry Frontiers · doi:10.1039/d4qi02385d · Cited by 82 · see citing works
Endogenous formaldehyde is a memory-related molecule in mice and humans
Ai, L., Tan, T., Tang, Y., Yang, J., Cui, D., Wang, R., Wang, A., Fei, X., Di, Y., Wang, X., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0694-x · Cited by 81 · see citing works
Formaldehyde toxicity in age-related neurological dementia
Kou, Y., Zhao, H., Cui, D., Han, H., & Tong, Z. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101512 · Cited by 79 · see citing works
Sulfur metabolism and its contribution to malignancy
Ward, N. P., & DeNicola, G. M. (2019) · International review of cytology · doi:10.1016/bs.ircmb.2019.05.001 · Cited by 74 · see citing works
Isonitrile-responsive and bioorthogonally removable tetrazine protecting groups
Tu, J., Svatunek, D., Parvez, S., Eckvahl, H. J., Xu, M., Peterson, R. T., Houk, K. N., & Franzini, R. M. (2019) · Chemical Science · doi:10.1039/c9sc04649f · Cited by 74 · see citing works
Reactive metabolite production is a targetable liability of glycolytic metabolism in lung cancer
Luengo, A., Abbott, K. L., Davidson, S. M., Hosios, A. M., Faubert, B., Chan, S. H., Freinkman, E., Zacharias, L. G., Mathews, T. P., Clish, C. B., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13419-4 · Cited by 73 · see citing works
Bruemmer, K. J., Green, O., Su, T. A., Shabat, D., & Chang, C. J. (2018) · Angewandte Chemie · doi:10.1002/ange.201802143 · Cited by 70 · see citing works
Self-citationReplication stress as a driver of cellular senescence and aging
Herr, L. M., Schaffer, E. D., Fuchs, K. F., Datta, A., & Brosh, R. M. (2024) · Communications Biology · doi:10.1038/s42003-024-06263-w · Cited by 68 · see citing works
Formaldehyde and Brain Disorders: A Meta-Analysis and Bioinformatics Approach
Rana, I., Rieswijk, L., Steinmaus, C., & Zhang, L.-P. (2021) · Neurotoxicity research · doi:10.1007/s12640-020-00320-y · Cited by 55 · see citing works
Chen, S., Jia, Y., Zou, G.-Y., Yu, Y., & Wang, J. (2019) · Nanoscale · doi:10.1039/c9nr00039a · Cited by 64 · see citing works
DNA-protein crosslink formation by endogenous aldehydes and AP sites
Nakamura, J., & Nakamura, M. (2020) · DNA repair · doi:10.1016/j.dnarep.2020.102806 · Cited by 64 · see citing works
Cycling back to folate metabolism in cancer
Lee, Y., Vousden, K. H., & Hennequart, M. (2024) · Nature Cancer · doi:10.1038/s43018-024-00739-8 · Cited by 65 · see citing works
Formate Induces a Metabolic Switch in Nucleotide and Energy Metabolism
Oizel, K., Tait-Mulder, J., Fernández-de-Cossio-Díaz, J., Pietzke, M., Brunton, H., Lilla, S., Dhayade, S., Athineos, D., Blanco, G. R., Sumpton, D. P., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-020-2523-z · Cited by 60 · see citing works
Self-citationZhao, S., Cordes, J., Caban, K. M., Götz, M. J., Mackens‐Kiani, T., Veltri, A. J., Sinha, N. K., Weickert, P., Kaya, S., Hewitt, G., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.10.012 · Cited by 60 · see citing works
Gao, W.-F., Zhang, X., Yang, W., Dou, D., Zhang, H., Tang, Y., Zhong, W., Meng, J., Bai, Y., Liu, Y., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0676-z · Cited by 59 · see citing works
Reciprocal Regulation of Metabolic Reprogramming and Epigenetic Modifications in Cancer
Yu, X., Ma, R., Wu, Y., Zhai, Y., & Li, S. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00394 · Cited by 61 · see citing works
Recent Progress in Fluorescent Formaldehyde Detection Using Small Molecule Probes
Zheng, J., Liu, W., Lu, F., Tang, Y., & Yuan, Z. (2022) · Journal of Analysis and Testing · doi:10.1007/s41664-022-00220-4 · Cited by 56 · see citing works
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Ma, C., Xia, F., & Kelley, S. O. (2020) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.0c00470 · Cited by 56 · see citing works
Ma, Y., Gao, W., Zhu, L., Zhao, Y., & Lin, W. (2019) · Chemical Communications · doi:10.1039/c9cc04411f · Cited by 55 · see citing works
Espadinha, D., Sobral, R. G., Mendes, C. I., Méric, G., Sheppard, S. K., Carriço, J. A., de LENCASTRE, H., & Miragaia, M. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.01971 · Cited by 53 · see citing works
Current state of research on non‐human primate models of Alzheimer’s disease
Li, H., Zhang, L., & Qin, C. (2019) · Animal Models and Experimental Medicine · doi:10.1002/ame2.12092 · Cited by 55 · see citing works
Shishodia, S., Zhang, D., El-Sagheer, A. H., Brown, T. P., Claridge, T. D. W., Schofield, C. J., & Hopkinson, R. J. (2018) · Organic & Biomolecular Chemistry · doi:10.1039/c8ob00734a · Cited by 54 · see citing works
Bioanalytical and Mass Spectrometric Methods for Aldehyde Profiling in Biological Fluids
Dator, R., Solivio, M. J., Villalta, P. W., & Balbo, S. (2019) · Toxics · doi:10.3390/toxics7020032 · Cited by 54 · see citing works
Endogenous toxic metabolites and implications in cancer therapy
Lee, N., Spears, M. E., Carlisle, A. E., & Kim, D. (2020) · Oncogene · doi:10.1038/s41388-020-01395-9 · Cited by 54 · see citing works
Ding, N., Li, Z., Hao, Y., & Yang, X. (2022) · Food Chemistry · doi:10.1016/j.foodchem.2022.132426 · Cited by 53 · see citing works
Cho, S. Y., Hwang, H., Kim, Y., Yoo, B. C., Han, N., Kong, S., Baek, M.-J., Kim, K., Lee, M. R., Park, J. G., et al. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.02.045 · Cited by 53 · see citing works
K6-linked ubiquitylation marks formaldehyde-induced RNA-protein crosslinks for resolution
Rahmanto, A. S., Blum, C., Scalera, C., Heidelberger, J. B., Mesitov, M. V., Horn‐Ghetko, D., Gräf, J. F., Mikičić, I., Hobrecht, R., Orekhova, A., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.10.011 · Cited by 52 · see citing works
Gao, G., Wang, J., Wang, X., Liu, G., Fan, L., Ru, G.-X., Wang, S., Song, M., Shen, W., Zheng, X. L., et al. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.2c03335 · Cited by 50 · see citing works
Wang, H., Xu, Y., Rao, L., Yang, C., Yuan, H., Gao, T., Chen, X., Sun, H., Xian, M., Liu, C., et al. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.8b05426 · Cited by 50 · see citing works
Reaction-based fluorescent and chemiluminescent probes for formaldehyde detection and imaging
Huang, S., Li, Z., Liu, M., Zhou, M., Weng, J., He, Y., Jiang, Y., Zhang, H., & Sun, H. (2022) · Chemical Communications · doi:10.1039/d1cc05644a · Cited by 48 · see citing works
Cellular responses to RNA damage
Cordes, J., Zhao, S., Engel, C. M., & Stingele, J. (2025) · Cell · doi:10.1016/j.cell.2025.01.005 · Cited by 51 · see citing works
Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction
Zhu, R., Zhang, G., Jing, M., Han, Y., Li, J., Zhao, J., Li, Y., & Chen, P. R. (2021) · Nature Communications · doi:10.1038/s41467-020-20754-4 · Cited by 48 · see citing works
Kiweler, N., Delbrouck, C., Pozdeev, V. I., Neises, L., Soriano‐Baguet, L., Eiden, K., Xian, F., Benzarti, M., Haase, L., Koncina, E., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30363-y · Cited by 45 · see citing works
Self-citationFappiano, L., Carriera, F., Iannone, A., Notardonato, I., & Avino, P. (2022) · Foods · doi:10.3390/foods11091351 · Cited by 46 · see citing works
Carcinogenesis of Male Oral Submucous Fibrosis Alters Salivary Microbiomes
Chen, M. Y., Chen, J.-W., Wu, L., Huang, K., Chen, J. Y., Wu, W., Chiang, W. F., Shih, C. J., Tsai, K. N., Hsieh, W., et al. (2020) · Journal of Dental Research · doi:10.1177/0022034520968750 · Cited by 46 · see citing works
Genotoxic aldehydes in the hematopoietic system
Wang, M., Dingler, F. A., & Patel, K. J. (2022) · Blood · doi:10.1182/blood.2019004316 · Cited by 49 · see citing works
Self-citationDing, N., Li, Z., Hao, Y., & Zhang, C. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.2c02166 · Cited by 44 · see citing works
Hao, Y., Zhang, Y., Zhang, A., Sun, Q., Zhu, J., Qu, P., Chen, S., & Xu, M. (2019) · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2019.117988 · Cited by 44 · see citing works
Zhang, Y., Du, Y. L., Li, M., Zhang, D., Xiang, Z., & Peng, T. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202001425 · Cited by 44 · see citing works
Du, Y. L., Zhang, Y., Huang, M., Wang, S., Wang, J., Liao, K., Wu, X., Zhou, Q., Zhang, X., Wu, Y., et al. (2021) · Chemical Science · doi:10.1039/d1sc04387k · Cited by 44 · see citing works
Zhu, H., Zhang, X., Liu, C., Zhang, Y., Su, M., Rong, X., Wang, X., Liu, M., Zhang, X., Sheng, W., et al. (2022) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2022.131962 · Cited by 44 · see citing works
Wang, M., Liu, Q., Sun, X., Zheng, S., Ma, Y., Wang, Y., Yan, M., Lü, Z., Fan, C., & Lin, W. (2021) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2021.129649 · Cited by 43 · see citing works
Modulation of DNA methylation by one-carbon metabolism: a milestone for healthy aging
Choi, S., & Friso, S. (2023) · Nutrition Research and Practice · doi:10.4162/nrp.2023.17.4.597 · Cited by 47 · see citing works
Polymers for Fluorescence Imaging of Formaldehyde in Living Systems via the Hantzsch Reaction
Liu, G., Shegiwal, A., Zeng, Y., Wei, Y., Boyer, C. A., Haddleton, D. M., & Tao, L. (2018) · ACS Macro Letters · doi:10.1021/acsmacrolett.8b00697 · Cited by 43 · see citing works
Wang, H., Wei, J., Zhang, C., Zhang, Y., Zhang, Y., Li, L., Yu, C., Zhang, P., & Chen, J. (2019) · Chinese Chemical Letters · doi:10.1016/j.cclet.2019.09.021 · Cited by 43 · see citing works
Formaldehyde and De/Methylation in Age-Related Cognitive Impairment
Li, T., Yan, W., Qu, M., Mou, L., Jun-Ye, M. I. A. O., Xi, M., Liu, Y., & He, R. (2021) · Genes · doi:10.3390/genes12060913 · Cited by 43 · see citing works
Spencer, P. S. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00754 · Cited by 42 · see citing works
Nakamura, J., Holley, D., Kawamoto, T., & Bultman, S. J. (2020) · Genes and Environment · doi:10.1186/s41021-020-00160-4 · Cited by 42 · see citing works
Xin, F., Tian, Y., Gao, C., Guo, B., Wu, Y., Zhao, J., Jing, J., & Zhang, X. (2018) · The Analyst · doi:10.1039/c8an02108b · Cited by 41 · see citing works
Fanconi anemia and the underlying causes of genomic instability
Rageul, J., & Kim, H. (2020) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22358 · Cited by 41 · see citing works
Review: Vaccine Myth-Buster – Cleaning Up With Prejudices and Dangerous Misinformation
Löffler, P. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.663280 · Cited by 42 · see citing works
Deciphering Functions of Intracellular Formaldehyde: Linking Cancer and Aldehyde Metabolism
Hopkinson, R. J., & Schofield, C. J. (2018) · Biochemistry · doi:10.1021/acs.biochem.7b01304 · Cited by 41 · see citing works
Subcellular one carbon metabolism in cancer, aging and epigenetics
Bernasocchi, T., & Mostoslavsky, R. (2024) · Frontiers in Epigenetics and Epigenomics · doi:10.3389/freae.2024.1451971 · Cited by 42 · see citing works
Nadalutti, C. A., Stefanick, D. F., Zhao, M., Horton, J. K., Prasad, R., Brooks, A. M., Griffith, J. D., & Wilson, S. H. (2020) · Scientific Reports · doi:10.1038/s41598-020-61477-2 · Cited by 40 · see citing works
Duan, Y., He, K., Zhang, G., & Hu, J. (2021) · Biomacromolecules · doi:10.1021/acs.biomac.1c00251 · Cited by 39 · see citing works
Prolonged persistence of mutagenic DNA lesions in somatic cells
Chapman, M. S., Mitchell, E., Yoshida, K., Williams, N., Fabre, M. A., Ranzoni, A. M., Robinson, P. S., Kregar, L. D., Wilk, C. M., Boettcher, S., et al. (2025) · Nature · doi:10.1038/s41586-024-08423-8 · Cited by 37 · see citing works
Chen, X., Legrand, A. J., Cunniffe, S. M. T., Hume, S., Poletto, M., Vaz, B., Ramadan, K., Yao, D., & Dianov, G. L. (2018) · Cellular Oncology · doi:10.1007/s13402-018-0390-8 · Cited by 38 · see citing works
Tao, R., Liao, M., Wang, Y., Wang, H., Tan, Y., Qin, S., Wei, W., Tang, C., Liang, X., Han, Y., et al. (2021) · Analytical Chemistry · doi:10.1021/acs.analchem.1c04520 · Cited by 38 · see citing works
Smaga, L. P., Pino, N. W., Ibarra, G. E., Krishnamurthy, V. V., & Chan, J. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.9b11899 · Cited by 37 · see citing works
Dorokhov, Y. L., Sheshukova, E. V., Евгеньевна, Б. Т., & Komarova, T. V. (2018) · BioEssays · doi:10.1002/bies.201800136 · Cited by 36 · see citing works
Bruemmer, K. J., Crossley, S. W. M., & Chang, C. J. (2019) · Angewandte Chemie · doi:10.1002/ange.201909690 · Cited by 36 · see citing works
Self-citationFormation and repair of unavoidable, endogenous interstrand cross-links in cellular DNA
Housh, K., Jha, J. S., Haldar, T., Amin, S. B. M., Islam, T., Wallace, A., Gomina, A., Guo, X., Nel, C., Wyatt, J. W., et al. (2020) · DNA repair · doi:10.1016/j.dnarep.2020.103029 · Cited by 36 · see citing works
Aldehyde-induced DNA-protein crosslinks- DNA damage, repair and mutagenesis
Blouin, T., & Saini, N. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1478373 · Cited by 35 · see citing works
Topoisomerase I-driven repair of UV-induced damage in NER-deficient cells
Saha, L. K., Wakasugi, M., Akter, S., Prasad, R., Wilson, S. H., Shimizu, N., Sasanuma, H., Huang, S.-Y. N., Agama, K., Pommier, Y. G., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1920165117 · Cited by 36 · see citing works
Chu, Z.-X., Song, Q., Zhang, Y., & Jiang, J. (2023) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2023.215338 · Cited by 35 · see citing works
Tan, L., Ding, H., Chanmungkalakul, S., Peng, L., Yuan, G., Yang, Q., Liu, X., & Zhou, L. (2021) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2021.130331 · Cited by 34 · see citing works
(De)Toxifying the Epigenetic Code
Zheng, Q., Prescott, N. A., Maksimovic, I., & David, Y. (2019) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.9b00013 · Cited by 34 · see citing works
Imaging of formaldehyde fluxes in epileptic brains with a two-photon fluorescence probe
Chen, J., Shao, C., Wang, X., Gu, J., Zhu, H., & Qian, Y. (2020) · Chemical Communications · doi:10.1039/d0cc00676a · Cited by 33 · see citing works
Bazurto, J. V., Nayak, D. D., Ticak, T., Davlieva, M. G., Lee, J. A., Hellenbrand, C. N., Lambert, L. B., Benski, O. J., Quates, C. J., Johnson, J. L., et al. (2021) · PLoS Biology · doi:10.1371/journal.pbio.3001208 · Cited by 33 · see citing works
Metformin Is a Pyridoxal-5′-phosphate (PLP)-Competitive Inhibitor of SHMT2
Tramonti, A., Cuyàs, E., Encinar, J. A., Pietzke, M., Paone, A., Verdura, S., Arbusà, A., Martı́n-Castillo, B., Giardina, G., Joven, J., et al. (2021) · Cancers · doi:10.3390/cancers13164009 · Cited by 31 · see citing works
Self-citation
- Authors
- Burgos-Barragan, G., Wit, N., Meiser, J., Dingler, F. A., Pietzke, M., Mulderrig, L., Pontel, L. B., Rosado, I. V., Brewer, T. F., Cordell, R. L., Monks, P. S., Chang, C. J., Vazquez, A., & Patel, K. J.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Cancer Research UK Scotland Institute (GB)
- Howard Hughes Medical Institute (US)
- University of Leicester (GB)
- Corresponding author
- Patel, Ketan J.
- ORCID
- Venue
- Nature
- Published
- 2017-08-16
- Volume
- 548
- Issue
- 7669
- Pages
- 549-554
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5714256
- OpenAlex
- W2748677962
- Cited by
- 359
- References
- 36
- Citations by year
- 2026: 29 · 2025: 48 · 2024: 50 · 2023: 38 · 2022: 42 · 2021: 40 · 2020: 44 · 2019: 42 · 2018: 24 · 2017: 2
- FWCI
- 26.78
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-08-23)
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Funders
- Wellcome Trust (106202, 106202/Z/14/Z)
- Cancer Research UK (23273, A18076, A21140, C596/A21140, A13647, 21140)
- European Commission
- Deutsche Forschungsgemeinschaft (ME 4636/2-1)
- National Institutes of Health (79465)
- Medical Research Council
- Engineering and Physical Sciences Research Council
- National Institute of General Medical Sciences (T32GM066698, R01GM079465)
- National Institute of Environmental Health Sciences (P42ES004705, R01ES028096)
- Topics
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- formaldehyde detoxification, one-carbon metabolism, folic acid, tetrahydrofolate, ADH5, alcohol dehydrogenase, formate, nucleotide synthesis, DNA cross-linking, genotoxicity, cancer therapy
- MeSH terms
- Alcohol Dehydrogenase, Animals, Carbon, Cell Line, Chickens, Coenzymes, Cross-Linking Reagents, DNA Damage, DNA Repair, Folic Acid, Formaldehyde, Humans, Inactivation, Metabolic, Mutagens, Nucleotides, Oxidation-Reduction, Serine, Tetrahydrofolates, Mice, Metabolic Networks and Pathways
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