Possible Role for Thymine Glycol in the Selective Inhibition of DMA Synthesis on Oxidized DMA Templates1 *'**

Single-stranded DMA of coliphage M13mp8 was treated with the oxidizing agent, KMn04, under conditions that selectively form c/'s-5,6-dihydro-5,6-dihydroxythymine (thymine glycol). Treatment of DMA with 0.7 and 1.4 HIM KMnO< introduced approximately 200 and 400 thymine glycol residues, respectively, per genome. When these DMAs were used to transform Escherichia coli, it was observed that phage survival was reduced in a dose-dependent manner. In studies designed to investigate the effect of DNA oxidation products on replication in vitro, a complementary 15-mer oligodeoxynucleotide was annealed to the oxidized template and extended with the Klenow fragment of DNA polymerase I from E. coli. It was observed that lesions in oxidized DNA strongly inhibited DNA elongation and that DNA synthesis was stopped opposite thymine residues. This is taken as suggestive evidence that the thymine glycol is inhibitory to DNA replication.