Telomere Structure In Drosophila

Environmental Health Sciences

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Abstract

In Drosophila, chromosome ends are maintained by the targeted transposition of two retrotransposons, HeT-A and TART. In the wild type, the frequency of transposition is sufficient to balance the gradual chromosome shortening due to incomplete DNA replication. Mutations are known that drastically increase or decrease the frequency of HeT-A addition to a chromosome end, suggesting that this process is under genetic control. We have characterized one such mutation, and we are using positional information to clone the gene. A transgene inserted into the telomere between the subterminal telomere associated sequence (TAS) and the terminal HeT-A/TART array is repressed and variegates. This variegation, termed telomeric position effect, TPE, appears to be due to an interaction of repression induced by TAS and activation initiated by HeT-A. A w+ transgene thus provides an assay for HeT-A transcription. These transgenes may provide a means to investigate the control of HeT-A transcription and transposition, and thus telomere elongation. We have found that w+ activity varies with changes in TAS sequences on the homologous telomere, as well as at other telomeres. Defects in, or deletions of, one of these TAS arrays increase w+ activity, and by extension HeT-A transcription. This may provide a means to increase transposition when one or more telomeres become abnormally short. With the goal of identifying proteins that play a role in this process, we screened autosomal deficiencies for dominant effects on TPE. Several suppressors were found, but the majority of these suppressors on chromosome 2 mapped to the left end of the chromosome, near the telomere and were associated with deletions of the 2L TAS. Analysis of chromosome 3 suppressors is in progress.