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. This mutator greatly reduces the efficacy of a repair pathway for 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 by other repair mechanisms, but are not replicated effectively and DNA sequences are lost from the capped ends. The DNA at the ends of several of these chromosomes have been sequenced and found to have no DNA distal to the genomic breakpoint. This observation suggests that proper replication of the chromosomal end may require a specific telomeric DNA sequence that has been described by others, but that chromosome viability is determined by a non-DNA component of the telomere. Stable derivatives of the capped ends have been isolated and found to have gained a telomere specific DNA sequence. These stable ends are being characterized. We are also developing a rapid assay for the mutator to facilitate genetic analysis and are investigating cell specificity of mutator activity.