Telomere Structure In Drosophila

Environmental Health Sciences

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Abstract

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 identified one gene, Telomere elongation, that increases the frequency of terminal gene conversion, and are using positional information to clone the gene. Sequencing of two independent mutant stocks suggests the mutant produces a truncated form of a DNA repair protein. While individuals with the Telomere elongation mutation do not appear to have decreased fitness, individuals with long terminal retrotransposon arrays have decreased fertility.[unreadable] Mutations in the mutator gene, mu2, increase the frequency of mutant chromosomes that have lost a telomere and reconstituted a structure that protects the chromosome end. We have shown that the MU2 protein interacts with the chromatin proteins HP1 and phosphorylated H2Av, the Drosophila orthologue of human H2AX. MU2 accumulates at DNA repair foci, and mutations in the gene interfere with the formation of foci. Sequence alignments suggest that mu2 is homologous to the human MDC1 gene. In an attempt to understand the interaction of factors that control telomere stability, we are making double mutation combinations of mu2 with 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 in these double mutant lines.