Induction of large DNA deletions by persistent nicks: a new hypothesis

DNA deletions of more than one or two base pairs are induced frequently enough so that these form a reasonable fraction of mutations for only a few mutagens. Of these agents, some such as ionizing radiations form DNA double-strand breaks, and very large deletions are thought to result from a DNA end from one break ligating with a second break on the 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 on induced deletions in particular Escherichia coli strains suggest a process involving a single lesion that could explain several features of large deletions: frequent occurrence in mammalian cells and scarcity in prokaryotes, nonrandom location which is perhaps associated with locations of origins of replication, and differences in the fraction of deletions among mutations in various genes. Some agents inducing deletions make single-strand nicks, not double-strand breaks, and the proposed mechanism hypothesizes that the inducing lesion is a persistent nick in one DNA strand--for example, a radiation-induced single-strand break with associated damage on the complementary strand that interferes with repair.