Telomere Structure In Drosophila

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Summary of Work: Telomeres are structures on the ends of chromosomes that are required for genome stability. Drosophila telomeres lack the simple repeats found in most species. Instead, Drosophila ends are maintained by tip specific transposition of a non-LTR retrotransposon family, HeT-A. Adjacent to the terminal transposon array is a telomere associated satellite (TAS) that resembles subtelomeric sequences in other species. The TAS repeats may inactivate genes placed in their vicinity and form associations with other telomeres. In many cases a reporter gene in TAS is repressed when the other telomeres are wild type, but less repressed when any other telomere is disrupted by an insertion into TAS or a deletion of TAS. We propose that the telomeres associate with each other at TAS, and that disruption of one telomere signals the retrotransposons on other telomeres to transcribe, resulting in relaxed chromatin around the transgene. Mutations of zeste, a pairing-dependent transcription factor, disrupt this interaction, supporting the hypothesis of physical interactions among telomeres affecting gene expression. This provides a mechanism to control HeT-A retrotransposition and thus telomere elongation. In a related project, trans-acting suppressers of telomeric repression in Drosophila are being characterized. Suppressers of telomeric silencing map to all the major chromosomes; several are homozygous lethal, suggesting they perform a vital functions. They suppress the activity of genes inserted into various telomeres, but not genes inserted into centromeric heterochromatin. They also have no effect on long-term developmental silencing, suggesting that they represent a new class of chromosomal protein. Mutations in the suppressor genes show a complex complementation pattern, suggesting that the encoded proteins form a complex to function.