Genetic and molecular analysis of terminal deletions of chromosome 3R of Drosophila melanogaster.

Terminal deletions of chromosome 3R are induced at a high frequency (3.2 x 10(-3)) by irradiating 45-4 Drosophila melanogaster females with a low dose of X-rays. The 45-4 line carries a white transgene inserted at 16 kb from the terminus and is homozygous for the mu-2 mutation, a gene involved in the repair of double-strand DNA breaks. Four of the 51 recovered deleted strains have lost modulo, the distalmost essential gene on chromosome 3R. Breakpoints of 22 deletions have been localised in a single hybridisation step, using pulsed-field gel electrophoresis to separate genomic DNA fragments obtained from digestion with a rare-cutter restriction enzyme. Breaks do not occur at random, but are rather clustered in three susceptible chromosomal domains. Backcross experiments resulting in transheterozygous (deleted chromosome/45-4) animals indicate that the activity of the white transgene is enhanced when the DNA break has occurred proximal to a critical position. This suggests that homologous chromosomal pairing distal to the critical position results in the definition of a more compact chromatin structure and, due to position effect, in the silencing of white.