CYTOGENETIC ANALYSIS OF MUTAGEN-SENSITIVE MUTANTS

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Mutants defective in DNA repair have been collected in Drosophila melanogaster and characterized cytogenetically in order to gain a basic understanding of the genetic control of sensitivity to mutagenic agents. Most of our recent work has centered on the mutants for the mei-9 and mei-41 genes. These mutants are sensitive to a wide variety of mutagenic agents, defective in excision and post replication repair respectively, and meiotic recombination, and have fragile chromosomes. The mei-41 gene is a hot spot for EMS and P-element insertion mutagenesis and shows a high frequency of interallelic meiotic recombination, suggesting that the gene is relatively large. To confirm this hypothesis and to better understand the structure and regulation of genes controlling DNA repair, these two genes have been cloned and are being characterized molecularly. The mei-41 gene controls the activity of a specific DNA endo- exonuclease that is antigenically related to endo- exonucleases from yeast and Neurospora. A DNA sequence that coded for the nuclease in yeast has been hybridized in situ to Drosophila salivary gland chromosomes. A single site of hybridization has been identified in region 56D on chromosome 2; mei-41, however, is located in region 14C on the X chromosome. We are currently cloning the gene using the yeast sequence as a probe.