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CDA directs metabolism of epigenetic nucleosides revealing a therapeutic window in cancer

Author

Listed:
  • Melania Zauri

    (Ludwig Cancer Research, University of Oxford)

  • Georgina Berridge

    (Target Discovery Institute, University of Oxford)

  • Marie-Laëtitia Thézénas

    (Target Discovery Institute, University of Oxford)

  • Kathryn M. Pugh

    (Target Discovery Institute, University of Oxford
    Structural Genomics Consortium, University of Oxford)

  • Robert Goldin

    (Centre for Pathology, Imperial College)

  • Benedikt M. Kessler

    (Target Discovery Institute, University of Oxford)

  • Skirmantas Kriaucionis

    (Ludwig Cancer Research, University of Oxford)

Abstract

Enzymes of the nucleotide salvage pathway are shown to have substrate selectivity that protects newly synthesized DNA from random incorporation of epigenetically modified forms of cytosine; a subset of cancer cell lines that overexpress cytidine deaminase (CDA) are sensitive to treatment with 5hmdC or 5fdC (oxidized forms of 5-methyl-cytosine), which leads to DNA damage and cell death, indicating the chemotherapeutic potential of these nucleoside variants for CDA-overexpressing cancers.

Suggested Citation

  • Melania Zauri & Georgina Berridge & Marie-Laëtitia Thézénas & Kathryn M. Pugh & Robert Goldin & Benedikt M. Kessler & Skirmantas Kriaucionis, 2015. "CDA directs metabolism of epigenetic nucleosides revealing a therapeutic window in cancer," Nature, Nature, vol. 524(7563), pages 114-118, August.
    • Handle: RePEc:nat:nature:v:524:y:2015:i:7563:d:10.1038_nature14948
    DOI: 10.1038/nature14948
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