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DNA modifications walk a fine line between epigenetics and mutagenesis

Nature Reviews Molecular Cell Biology volume 24, pages 449–450 (2023)Cite this article

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In the study of DNA modifications, the disciplines of epigenetics and of DNA damage and repair have evolved separately. The lines are now blurred by the realization that epigenetic modifications require DNA repair pathways for erasure and by the recent discoveries that oxidative DNA damage can upregulate gene expression.

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References

  1. Wang, D. et al. Active DNA demethylation promotes cell fate specification and the DNA damage response. Science 378, 983–989 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mattei, A. L., Bailly, N. & Meissner, A. DNA methylation: a historical perspective. Trends Genet. 38, 676–707 (2022).

    Article  CAS  PubMed  Google Scholar 

  3. Fleming, A. M. & Burrows, C. J. Oxidative stress-mediated epigenetic regulation by G-quadruplexes. NAR Cancer 3, zcab038 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  4. David, S. S. & Williams, S. D. Chemistry of glycosylases and endonucleases involved in base-excision repair. Chem. Rev. 98, 1221–1262 (1998).

    Article  CAS  PubMed  Google Scholar 

  5. Perillo, B. et al. DNA oxidation as triggered by H3K9me2 demethylation drives estrogen-induced gene expression. Science 319, 202–206 (2008).

    Article  CAS  PubMed  Google Scholar 

  6. Fleming, A. M., Ding, Y. & Burrows, C. J. Oxidative DNA damage is epigenetic by regulating gene transcription via base excision repair. Proc. Natl Acad. Sci. USA 114, 2604–2609 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Pan, L. et al. Oxidized guanine base lesions function in 8-oxoguanine DNA glycosylase1-mediated epigenetic regulation of nuclear factor kappaB-driven gene expression. J. Biol. Chem. 291, 25553–25566 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Spiegel, J. et al. G-quadruplexes are transcription factor binding hubs in human chromatin. Genome Biol. 22, 117 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pfaffeneder, T. et al. Tet oxidizes thymine to 5-hydroxymethyluracil in mouse embryonic stem cell DNA. Nat. Chem. Biol. 10, 574–581 (2014).

    Article  CAS  PubMed  Google Scholar 

  10. Simmen, M. W. Genome-scale relationships between cytosine methylation and dinucleotide abundances in animals. Genomics 92, 33–40 (2008).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Research on this topic in our laboratory has been supported by the National Cancer Institute (R01 CA090689) and the National Institute of General Medical Sciences (R35 GM145237).

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  1. Department of Chemistry, University of Utah, Salt Lake City, UT, USA

    Aaron M. Fleming & Cynthia J. Burrows

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  1. Aaron M. Fleming
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  2. Cynthia J. Burrows
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Correspondence to Cynthia J. Burrows.

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The authors declare no competing interests.

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Fleming, A.M., Burrows, C.J. DNA modifications walk a fine line between epigenetics and mutagenesis. Nat Rev Mol Cell Biol 24, 449–450 (2023). https://doi.org/10.1038/s41580-023-00590-2

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