Molecular cloning and tissue-specific expression of the mutator2 gene (mu2) in Drosophila melanogaster

We present here the molecular cloning and characterization of the mutator2 (mu2) gene of Drosophila melanogaster together with further genetic analyse s of its mutant phenotype. mu2 functions in oogenesis during meiotic recomb ination, during repair of radiation damage in mature oocytes, and in prolif erating somatic cells, where mu2 mutations cause an increase in somatic rec ombination. Our data show that mu2 represents a novel component in the proc essing of double strand breaks (DSBs) in female meiosis. mu2 does not code for a DNA repair enzyme because mu2 mutants are not hypersensitive to DSB-i nducing agents. We have mapped and cloned the mu2 gene and rescued the mu2 phenotype by germ-line transformation with genomic DNA fragments containing the mu2 gene. Sequencing its cDNA demonstrates that mu2 encodes a novel 13 9-kD protein, which is highly basic in the carboxy half and carries three n uclear localization signals and a helix-loop-helix domain. Consistent with the sex-specific mutant phenotype, the gene is expressed in ovaries but not in testes. During oogenesis its RNA is rapidly transported from the nurse cells into the oocyte where it accumulates specifically at the anterior mar gin. Expression is also prominent in diploid proliferating cells of larval somatic tissues. Our genetic and molecular data are consistent with the mod el that mu2 encodes a structural component of the oocyte nucleus. The MU2 p rotein may be involved in controlling chromatin structure and thus may infl uence the processing of DNA DSBs.