Ribonucleotide reductase and thymidylate synthase or exogenous deoxyribonucleosides reduce DNA damage and senescence caused by C‐MYC depletion Public Deposited

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  • The down‐regulation of dominant oncogenes, including C‐MYC, in tumor cells often leads to the induction of senescence via mechanisms that are not completely identified. In the current study, we demonstrate that MYC‐depleted melanoma cells undergo extensive DNA damage that is caused by the underexpression of thymidylate synthase (TS) and ribonucleotide reductase (RR) and subsequent depletion of deoxyribonucleoside triphosphate pools. Simultaneous genetic inhibition of TS and RR in melanoma cells induced DNA damage and senescence phenotypes very similar to the ones caused by MYC‐depletion. Reciprocally, overexpression of TS and RR in melanoma cells or addition of deoxyribonucleosides to culture media substantially inhibited DNA damage and senescence‐associated phenotypes caused by C‐MYC depletion. Our data demonstrate the essential role of TS and RR in C‐MYC‐dependent suppression of senescence in melanoma cells.
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  • Mannava, S., Moparthy, K. C., Wheeler, L. J., Leonova, K. I., Wawrzyniak, J. A., Bianchi-Smiraglia, A., . . . Nikiforov, M. A. (2012). Ribonucleotide reductase and thymidylate synthase or exogenous deoxyribonucleosides reduce DNA damage and senescence caused by C-MYC depletion. Aging, 4(12), 917-922.
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  • description.provenance : Approved for entry into archive by Deanne Bruner(deanne.bruner@oregonstate.edu) on 2013-04-22T20:38:15Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: bb87e2fb4674c76d0d2e9ed07fbb9c86 (MD5) MathewsChristopherBiochemistryBiophysicsRibonucleotideReductaseThymidylate.pdf: 1708744 bytes, checksum: a7cc8b8e77da7c0d0c04eda8a60e1a9c (MD5)
  • description.provenance : Made available in DSpace on 2013-04-22T20:38:15Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: bb87e2fb4674c76d0d2e9ed07fbb9c86 (MD5) MathewsChristopherBiochemistryBiophysicsRibonucleotideReductaseThymidylate.pdf: 1708744 bytes, checksum: a7cc8b8e77da7c0d0c04eda8a60e1a9c (MD5) Previous issue date: 2012-12
  • description.provenance : Submitted by Deanne Bruner (deanne.bruner@oregonstate.edu) on 2013-04-22T20:36:33Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: bb87e2fb4674c76d0d2e9ed07fbb9c86 (MD5) MathewsChristopherBiochemistryBiophysicsRibonucleotideReductaseThymidylate.pdf: 1708744 bytes, checksum: a7cc8b8e77da7c0d0c04eda8a60e1a9c (MD5)

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