DNA synthesis is blocked by cigarette tar-induced DNA single-strand breaks

Abstract

DNA single-strand breaks are caused by aqueous extracts of cigarette tar, due to the reduction of oxygen to superoxide by tar and the subsequent production of hydroxyl radicals. The action of DNA metabolism enzymes on these single-strand breaks has been studied to probe the consequences of these lesions for DNA repair. Our results demonstrate that cigarette tar-induced nicks are blocked at the 3′ terminus since they are totally incapable of activating DNA for DNA synthesis by Escherichia coli DNA polymerase I. The 3′ termini of these tar-induced nicks are activated, however, for DNA synthesis by E. coli exonuclease III or by the 3′ phosphatase activity of T4 polynucleotide kinase. Because of the inability of tar-induced lesions to support DNA synthesis, they probably require a multi-step process for repair in vivo. As a consequence, the overall likelihood of mutation is increased due to the possibility for error at each step of the repair process.