We are interested in the genetic control of telomere structure and identity, and have focused on the model organism, Drosophila melanogaster. Telomeres in this organism are maintained by a combination of targeted retrotransposition of three LINE-like, transposons and gene conversion. 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 (Tel), 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 10 kb, inside an intron for the gene Ino80 and near five other genes in the same intron. 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. Deep sequencing the mutant and comparison with 180 wild type strains with short telomeres identified a single short, 3 bp deletion in this intronic region. This analysis also identified three new variant strains among the 180 control strains that have exceptionally long telomeres. 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 initiated a project to mark a telomere-specific HeT-A transposable element with a transcribed gene in order to follow the transposon as it moves from one chromosome end to another. A HeT-A element has been constructed inside a EPgy2 transposon and inserted into the genome of a fly to assay transposition in vivo. 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. Mass spectrometry of the Gag-like protein encoded by the HeT-A element reveals phosphorylation at serines 216 and 221. These modifications appear to play a role in protein stability.
|Capkova Frydrychova, R; Biessmann, H; Mason, J M (2008) Regulation of telomere length in Drosophila. Cytogenet Genome Res 122:356-64|