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

Melania Zauri, Georgina Berridge, Marie-Laëtitia Thézénas, Kathryn M. Pugh, Robert Goldin, Benedikt M. Kessler and Skirmantas Kriaucionis ()
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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
Robert Goldin: Centre for Pathology, Imperial College
Benedikt M. Kessler: Target Discovery Institute, University of Oxford
Skirmantas Kriaucionis: Ludwig Cancer Research, University of Oxford

Nature, 2015, vol. 524, issue 7563, 114-118

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.

Date: 2015
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DOI: 10.1038/nature14948

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