Determinants of dicentric chromosome breakage in Drosophila.

Eukaryotic genomes often have fragile sites where chromosomes are particularly prone to break. In Drosophila, when dicentric ring chromosomes try to segregate, they break at nonrandom hotspots. Here, we precisely map breakage hotspots produced by dicentric ring chromosomes in Drosophila. Our study provides three key results about the nature of dicentric chromosome breakage. First, duplications produced by dicentric ring chromosome breakage are surprisingly complex and involve many structural rearrangements, indicating that healing of these breaks is not a simple process. Second, characterization of one particular hotspot showed that new termini all occurred within a single intron of a large testis-expressed gene, suggesting that replication-transcription conflict may be a key determinant of chromosome fragile sites. Third, the new ends are often located near preexisting transposons, suggesting that transposon insertions may contribute to fragility or participate in stabilization of broken ends.