A Drosophila ribosomal protein contains 8-oxoguanine and abasic site DNA repair activities

Adly Yacoub, Laura Augeri, Mark R. Kelley, Paul W. Doetsch, Walter A. Deutsch

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Ionizing radiation and normal cellular respiration form reactive oxygen species that damage DNA and contribute to a variety of human disorders including tumor promotion and carcinogenesis. A major product of free radical DNA damage is the formation of 8-oxoguanine, which is a highly mutagenic base modification produced by oxidative stress. Here, Drosophila ribosomal protein S3 is shown to cleave DNA containing 8-oxoguanine residues efficiently. The ribosomal protein also contains an associated apurinic/apyrimidinic (AP) lyase activity, cleaving phosphodiester bonds via a β,δ elimination reaction. The significance of this DNA repair activity acting on 8-oxoguanine is shown by the ability of S3 to rescue the H2O2 sensitivity of an Escherichia coli mutM strain (defective for the repair of 8-oxoguanine) and to abolish completely the mutator phenotype of mutM caused by 8-oxoguanine-mediated G→T transversions. The ribosomal protein is also able to rescue the alkylation sensitivity of an E.coli mutant deficient for the AP endonuclease activities associated with exonuclease III (xth) and endonuclease IV (nfo), indicating for the first time that an AP lyase can represent a significant source of DNA repair activity for the repair of AP sites. These results raise the possibility that DNA repair may be associated with protein translation.

Original languageEnglish (US)
Pages (from-to)2306-2312
Number of pages7
JournalEMBO Journal
Volume15
Issue number9
StatePublished - May 1 1996

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Keywords

  • 8-oxoguanine
  • AP lyase
  • DNA repair
  • Mutagenesis
  • Oxidative stress

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Yacoub, A., Augeri, L., Kelley, M. R., Doetsch, P. W., & Deutsch, W. A. (1996). A Drosophila ribosomal protein contains 8-oxoguanine and abasic site DNA repair activities. EMBO Journal, 15(9), 2306-2312.