The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Serine Metabolism Supports the Methionine Cycle and DNA/RNA Methylation through De Novo ATP Synthesis in Cancer Cells
Open accessAbstract
Crosstalk between cellular metabolism and the epigenome regulates epigenetic and metabolic homeostasis and normal cell behavior. Changes in cancer cell metabolism can directly impact epigenetic regulation and promote transformation. Here we analyzed the contribution of methionine and serine metabolism to methylation of DNA and RNA. Serine can contribute to this pathway by providing one-carbon units to regenerate methionine from homocysteine. While we observed this contribution under methionine-depleted conditions, unexpectedly, we found that serine supported the methionine cycle in the presence and absence of methionine through de novo ATP synthesis. Serine starvation increased the methionine/S-adenosyl methionine ratio, decreasing the transfer of methyl groups to DNA and RNA. While serine starvation dramatically decreased ATP levels, this was accompanied by lower AMP and did not activate AMPK. This work highlights the difference between ATP turnover and new ATP synthesis and defines a vital function of nucleotide synthesis beyond making nucleic acids.
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Cites
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Linking DNA methylation and histone modification: patterns and paradigms
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“The function of methylation reactions is context and substrate dependent; for example, DNA and histone methylation are epigenetic modifications that have important influences on chromatin structure and regulation of gene expression (Cedar and Bergman, 2009; Gut and Verdin, 2013).”
BackgroundFunction and information content of DNA methylation
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IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype
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Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
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Cited by
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
Serine and one-carbon metabolism in cancer
Yang, M., & Vousden, K. H. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.81 · Cited by 992
Self-citationMechanisms and Implications of Metabolic Heterogeneity in Cancer
Kim, J., & DeBerardinis, R. J. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.08.013 · Cited by 606
Modulating the therapeutic response of tumours to dietary serine and glycine starvation
Maddocks, O. D. K., Athineos, D., Cheung, E. C., Lee, P., Zhang, T., van den Broek, N. J. F., Mackay, G. M., Labuschagne, C. F., Gay, D., Kruiswijk, F., et al. (2017) · Nature · doi:10.1038/nature22056 · Cited by 603
Self-citationThe role of methionine on metabolism, oxidative stress, and diseases
Martínez, Y., Li, X., Liu, G., Bin, P., Yan, W., Más, D., Valdivié, M., Hu, C.-A. A., Ren, W., & Yin, Y. (2017) · Amino Acids · doi:10.1007/s00726-017-2494-2 · Cited by 583
Metadata
- Authors
- Maddocks, O. D. K., Labuschagne, C. F., Adams, P. D., & Vousden, K. H.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 61
- Issue
- 2
- Pages
- 210-221
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2230238676
- Cited by
- 440
- References
- 14
- FWCI
- 19.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Maddocks, O. D. K., Labuschagne, C. F., Adams, P. D., & Vousden, K. H. (2016). Serine Metabolism Supports the Methionine Cycle and DNA/RNA Methylation through De Novo ATP Synthesis in Cancer Cells. Molecular Cell. https://doi.org/10.1016/j.molcel.2015.12.014
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