GENETIC CONTROL OF MUTATION IN DROSOPHILA

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This project is designed to determine the relationship between DNA repair, chromosome structure and mutagenesis in Drosophila melanogaster. A mutation that increases the mutation frequency (a mutator) has been identified and characterized. The mutator greatly reduces the efficacy of repair of x-ray induced chromosome breaks, thereby allowing a previously undescribed repair pathway to be observed. By this newly identified repair pathway broken chromosome ends are "capped" with a new telomere. The new chromosome ends are protected from degradation. These broken ends are not replicated effectively and DNA sequences are lost from the capped ends. Quasi-stable derivatives of the capped ends have been isolated and found to have gained a telomere-specific DNA sequence which has a structure resembling a retrotransposon. Preliminary evidence suggests that natural chromosome ends also recede because of incomplete DNA replication and occasionally lengthen by the acquisition of this telomere-specific sequence. The rate of loss is balanced by the rate of transposition to maintain chromosome length. We are also developing a rapid assay for the mutator to facilitate genetic analysis and investigating cell specificity of mutator activity. The mutator gene maps to polytene region 62B12-C1. Yeast artificial chromosomes that cover the region are being subcloned to identify a transcription unit that corresponds to the mutator gene.