Heteroduplex-induced mutagenesis in mammalian cells

We have shown previously that heteroduplexes containing single-stranded loops are repaired efficiently in monkey cells, but not always correctly: 2% of the repair products acquired mutations within a 350 base-pair target (Weiss, U. and Wilson, J.H., Proc. Natl. Acad. Sci. USA 87:1123-1126, 1987). The structures of the mutant genomes, which are described here, are consistent with an error-prone repair system. The spectrum of mutations includes about 25% point mutations and 75% rearrangements, which consist of deletions, duplications, and substitutions. The mutations are clustered in the vicinity of single-stranded loops in the original heteroduplex. The high frequency of mutation, their clustering, and the positions of rearrangement endpoints suggest that the mutations were generated during repair of the heteroduplexes.