Deletion formation in mammalian cells: molecular analysis of breakpoints and junctions in the hamster aprt locus

Abstract

To examine the mechanisms governing deletion formation in mammalian cells, we have analyzed the breakpoints and junction fragments produced by seven such mutations at the aprt locus of Chinese hamster ovary cells at the base sequence level. The deletions were heterogeneous both in size, varying from 38 bp to 170 kb, and in sequence in that no recurring sequence or structural motifs were evident. Most were simple exchanges at overlapping di- or trinucleotides, but one was the result of a complex rearrangement in which breakpoints approximately 34 kb apart were joined by 16- and 398-bp inserted fragments originating some distance from the target. Unlike many human germ line deletions, few of the breakpoints fell within hamster repetitive elements. The directionality of the deletions at aprt indicates that an essential gene or structure may determine the pattern of such mutations.