CYTOGENETIC ANALYSIS OF MUTAGEN-SENSITIVE MUTANTS

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Mutants of the mei-9 and mei-41 genes of Drosophila melanogaster are sensitive to a variety of mutagenic agents, defective in excision and postreplication 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 genes have been cloned using transposon tagging and are being characterized molecularly. The mei-41 transcript is 2.2 kilobase pairs in length and distributed over 14-28 kilobase pairs of genomic DNA. The mei-9 has not yet been cloned because multiple repeated sequences in the immediate region make molecular walking difficult. Another gene, mus3O8, has been identified based on increased sensitivity to mutagens and appears to be analogous with Fanconi's anemia, a human disorder associated with chromosome instability and an increased incidence of leukemia. This gene is also being cloned.