Region specific effects on chromosome integrity of mutants at essential loci in Drosophila melanogaster

Two mutagen-sensitive loci of Drosophila melanogaster, mus-105 and mus-109, previously identified by viable alleles, are shown to specify essential functions. Lethal alleles at the loci produce larvae that have degenerate imaginal discs and die at the larva-pupa boundary. Our data suggest that the causes of lethality are intolerable levels of cell death produced by high frequencies of chromosome aberrations (in excess of 0.5 aberration per cell per cycle). The pattern of aberrations is a locus-specific character. In mus-105 mutants the most common aberrations are breaks and exchanges in euchromatic portions of the genome whereas in mus-109 mutants the most common aberrations are breaks at heterochromatin-euchromatin junctions. The sensitivity of these junctions to breakage in mus-109 mutants is a property of all such junctions whether natural or produced by a rearrangement that juxtaposes heterochromatin and euchromatin. Larvae carrying the combination of two viable mutants, mus-105(A1) mus-109(D1), die at the larva-pupa boundary and display a high frequency of aberrations (0.7 per cell vs. 0.075 for either mutant alone) clustered at euchromatin-heterochromatin junctions. This synergistic interaction suggests there is a class of lesions that can be repaired by both mus-105(+) and mus-109(+). Thus, the apparent euchromatic specificity of mus-105(+), which was inferred from the pattern of predominantly euchromatic breakage observed in mus-105 mus-109(+) flies, is in fact generated by the wild-type function of mus-109(+) masking an effect of mus-105 in the heterochromatin. The fact that lethal mutants at the mus-105 and mus-109 loci have small imaginal discs coupled with the observation of a maternal effect of mus-105 suggests a paradigm for the control of cell division during the life cycle of Drosophila