The occurrence and consequences of deoxyuridine in DNA

R. G. Richards, L. C. Sowers, J. Laszlo, W. D. Sedwick

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Deoxyuridine can become resident in the DNA of prokaryotic and eukaryotic cells via two general mechanisms - deamination of cytosine to uracil, and nucleotide pool changes that lead to misincorporation of deoxyuridine in place of thymidine. In this paper we have examined the chemical basis of deamination reactions in DNA and discussed a possible mechanism for an increased rate of deamination by means of cross-strand protonation of cytosine by alkylated guanine. In addition, we have examined the genetic and drug-induced conditions that lead to dUMP misincorporation into DNA in place of thymidine and have presented experimental evidence indicating that the antifolate-induced lesion is a general drug-dose dependent lesion of human blood cells. Finally, the toxic and genetic impact of this lesion has been evaluated within the context of a review of the repair mechanisms elicited by dUMP in DNA.

Original languageEnglish (US)
Pages (from-to)157-185
Number of pages29
JournalAdvances in Enzyme Regulation
Volume22
Issue numberC
DOIs
StatePublished - 1984
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Cancer Research

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