Telomere Structure In Drosophila

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We are interested in the genetic control of telomere structure and identity, and have focused on the model organism, Drosophila melanogaster. Mutations in this organism are known that drastically increase or decrease the frequency of additions of telomere-specific retrotransposon to a chromosome end, suggesting that this process is under genetic control. We have identified one gene, Telomere elongation, which has mutations that increase the frequencies of both terminal gene conversion and targeted transposition, and are using positional information to clone the gene. The Tel gene maps to the middle of right arm of chromosome 3 to a region of approximately 55 kb, which includes five genes. Sequencing the coding regions of these genes did not identify a high probability candidate gene. The observations that the Tel mutations are genetically dominant and that deletions for the region do not have a telomere elongation phenotype suggest that the mutations are gain-of-function mutations and may be in controlling regions. Next generation DNA sequencing has identified three small indels in intergenic regions that are present in the mutant chromosome but not the wild type controls. Chromatin structure may regulate telomere length by controlling transcription of the telomeric retrotransposons and by controlling accessibility of the retroelements to the chromosome end. We have marked a HeT-A transposable element with a transcribed gene in order to follow the transposon as it moves from one chromosome end to another. The marked element has been transformed into animals, and we are attempting to force it to transpose to a chromosome end. If the assay works, it will allow us to investigate what genetic and environmental factors influence the rate of movement, either by classical retrotransposition or by telomeric gene conversion.