INDUCTION OF LARGE DNA DELETIONS BY PERSISTENT NICKS - A NEW HYPOTHESIS

DNA deletions of more than one or two base pairs are induced frequentl y enough so that these form a reasonable fraction of mutations for onl y a few mutagens. Of these agents, some such as ionizing radiations fo rm DNA double-strand breaks, and very large deletions are thought to r esult from a DNA end from one break ligating with a second break on th e same DNA molecule. However, deletions of kilobase pairs and more are sometimes induced by ionizing radiation at a higher rate than can be accounted for by the numbers of double-strand breaks. Published data o n induced deletions in particular Escherichia coli strains suggest a p rocess involving a single lesion that could explain several features o f large deletions: frequent occurrence in mammalian cells and scarcity in prokaryotes, nonrandom location which is perhaps associated with l ocations of origins of replication, and differences in the fraction of deletions among mutations in various genes. Some agents inducing dele tions make single-strand nicks, not double-strand breaks, and the prop osed mechanism hypothesizes that the inducing lesion is a persistent n ick in one DNA strand - for example, a radiation-induced single-strand break with associated damage on the complementary strand that interfe res with repair.