Telomere Structure In Drosophila

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Telomeres are nucleoprotein structures at chromosome ends that are required to completely replicate the linear DNA and to distinguish the natural chromosome end from a double strand chromosome break for purposes of DNA repair. In Drosophila, chromosome ends are maintained by the targeted transposition of three retrotransposons, HeT-A, TAHRE, and TART, as well as gene conversion between telomeres. In the wild type, transposition and gene conversion are sufficient to balance the gradual chromosome shortening due to incomplete DNA replication. Mutations are known that drastically increase or decrease the frequency of retrotransposon addition to a chromosome end, suggesting that this process is under genetic control. We have characterized one mutation that increases the frequency of terminal gene conversion, and are using positional information to clone the gene. A transgene inserted into a telomere is subject to repression, termed telomere position effect, TPE. TPE is found in a wide variety of species, including yeast, insects, and humans. In Drosophila, a transgene in the subterminal telomere associated sequence (TAS), or between TAS and the terminal retrotransposon array is repressed and variegates. This variegation appears to be due to an interaction of repression induced by TAS and activation initiated by HeT-A transcription. A telomeric transgene thus provides an assay for this interaction. These transgenes may provide a means to investigate the control of HeT-A transcription and transposition, and thus telomere elongation. Transgenes inserted into TAS behave as if they were in heterochromatin, while similar transgenes in the terminal retrotransposon array express at a level consistent with insertions into euchromatin. Mutations are known that drastically increase or decrease the frequency of retrotransposon addition to a chromosome end, suggesting that this process is under genetic control. We have characterized one mutation that increases the transposon array length by increasiing the frequency of terminal gene conversion, and are using positional information to clone the gene. Individuals with long terminal retrotransposon arrays have decreased fertility. In an attempt to understand the interaction of factors that control telomere stability, we are making double mutation combinations with the mutator, mu2, which increases the frequency of one-break deletions that have lost a natural telomere and formed a new telomere on the broken end. The second mutation will be a mutation that decreases telomere stability and increases telomere fusions. We will test both the generation of new telomeres and the frequency of telomere fusions.