Ionizing radiation and oxidizing agents form many damages in common in DNA. Some of the lesions are potentially mutagenic or carcinogenic. Little is currently known about whether or how most of these damages are enzymatically repaired, or what other responses they prompt in living cells. This problem will be addressed by taking advantage of DNA glycoslases that release specific products from oxidized DNA, and of a newly discovered inducible resistance to oxidizing agents and ionizing radiation. The glycosylases and sensitive chemical assays will allow us to assess the repair or persistence of a number of important oxidation lesions in cellular DNA under a variety of conditions, and the relationship of these to mutagenesis and toxicity. The peroxide-induced resistance to oxidation and radiation in E. coli is a key to determining the importance of known enzymes in repair of oxidized DNA, and to locating and molecular cloning of genes important in cellular recovery from oxidation and radiation. It will be investigated whether a similar induced response exists in eukaryotic cells, notably yeast. Known E. coli and yeast genes will be assessed for their importance in constitutive or induced resistance to oxidation. It will also be tested whether oxidation induces promiscuous or illegitimate recombinations. The results will have a direct bearing on deciding the biological effects of oxidation and of low-level radiation damage to DNA.
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