DNA repair defects and other mustakes in Drosophila melanogaster

Preservation of the structural integrity of DNA in any organism is crucial to its health and survival. Such preservation is achieved by an extraordina ry cellular arsenal of damage surveillance and repair functions, many of wh ich are now being defined at the gene and protein levels. Mutants hypersens itive to the killing effects of DNA-damaging agents have been instrumental in helping to identify DNA repair-related genes and to elucidate repair mec hanisms. In Drosophila melanogaster, such strains are generally referred to as mutagen-sensitive (mus) mutants and currently define more than 30 genet ic loci. Whereas most mus mutants have been recovered on the basis of hyper sensitivity to the monofunctional alkylating agent methyl methanesulfonate, they nevertheless constitute a phenotypically diverse group, with many mut ants having effects beyond mutagen sensitivity. These phenotypes include me iotic dysfunctions, somatic chromosome instabilities, chromatin abnormaliti es, and cell proliferation defects. Within the last few years numerous mus and other DNA repair-related genes of Drosophila have been molecularly clon ed, providing new insights into the functions of these genes. This article outlines strategies for isolating mus mutations and reviews recent advances in the Drosophila DNA repair field, emphasizing mutant analysis and gene c loning. (C) 1999 Academic Press.