Telomeres are the ends of eukaryotic chromosomes and are thought to be specialized for several vital functions. This application evaluates the hypothesis that Drosophila has telomeres with a structure fundamentally different from that reported for other eukaryotes. Simple-sequence tandem repeats are a ubiquitous feature of the DNA at the chromosomal termini of many phylogenetically diverse eukaryotes, including man. These repeats have been shown to be necessary and sufficient for telomere functions in yeast. A terminus of a Drosophila chromosome has been isolated and found to lack this terminal repeat motif. One of the specific aims of this proposal is to isolate this terminus from other strains of Drosophila to confirm that the first terminus examined is typical and has not lost the normal telomere by mutation. The terminal region will be isolated from recombinant libraries of the genomic DNA of other strains by hybridization with a subterminal unique sequence probe. The Drosophila terminus which has been isolated has a region of complex repetitive sequences, probably including a portion of a retrotransposon, at the end. Complex repeats are common in the subterminal regions of the chromosomes of other eukaryotes, but have no established functions and are thought to be dispensable. In Drosophila, these complex repeats may be providing telomere functions in lieu of conventional telomeric repeats. However, there is a progressive loss of the terminal sequences from the end of this chromosome.
A second aim of the proposal is to test the predictions of a hypothesis that the slow terminal loss is balanced by occasional transpositions of retrotransposons to the terminus. In situ hybridization will be used to test whether the putative retrotransposon already isolated from one terminus is often found near other termini. Identification of remnants of other retrotransposons within the complex terminal repeat region is also proposed. This will be done by screening the terminal region DNA clones for sequences conserved among retrotransposon genes encoding reverse transcriptase-related proteins. Furthermore, terminal additions capping terminal deletions will be studied to see whether these involve terminal transpositions of retrotransposons.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM038259-04A2
Application #
3294497
Study Section
Genetics Study Section (GEN)
Project Start
1987-04-01
Project End
1994-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
Maxwell, Patrick H; Belote, John M; Levis, Robert W (2008) Developmental and tissue-specific accumulation pattern for the Drosophila melanogaster TART ORF1 protein. Gene 415:32-9
Maxwell, Patrick H; Belote, John M; Levis, Robert W (2006) Identification of multiple transcription initiation, polyadenylation, and splice sites in the Drosophila melanogaster TART family of telomeric retrotransposons. Nucleic Acids Res 34:5498-507
Sheen, F M; Levis, R W (1994) Transposition of the LINE-like retrotransposon TART to Drosophila chromosome termini. Proc Natl Acad Sci U S A 91:12510-4
Levis, R W (1993) Drosophila melanogaster does not share the telomeric repeat sequence of another invertebrate, Ascaris lumbricoides. Mol Gen Genet 236:440-2
Levis, R W; Ganesan, R; Houtchens, K et al. (1993) Transposons in place of telomeric repeats at a Drosophila telomere. Cell 75:1083-93
Biessmann, H; Valgeirsdottir, K; Lofsky, A et al. (1992) HeT-A, a transposable element specifically involved in ""healing"" broken chromosome ends in Drosophila melanogaster. Mol Cell Biol 12:3910-8
Runkel, N S; Moody, F G; Smith, G S et al. (1991) The role of the gut in the development of sepsis in acute pancreatitis. J Surg Res 51:18-23
Levis, R W (1989) Viable deletions of a telomere from a Drosophila chromosome. Cell 58:791-801