of Work: Telomeres are structures on the ends of linear chromosomes that are required for genome stability. They counterbalance the loss of DNA from a chromosome end due to incomplete DNA replication and they distinguish a natural chromosome end from a broken chromosome end. Drosophila Telomeres lack the simple tandem repeats found at telomeres in most species. Instead, Drosophila ends are maintained by tip specific transposition of a non-LTR retrotransposon. Adjacent to this transposon array is a telomere associated satellite (TAS) that resembles subtelomeric sequences in other species. The TAS repeats are thought to be associated with the formation of heterochromatin and the inactivation of genes placed in their vicinity, and may be instrumental in forming associations with other telomeres, the nuclear matrix and the lamina. Reporter genes placed in TAS are repressed and variegate, that is they are expressed in some cells of the appropriate tissue, but not others. In many cases a reporter gene inserted into TAS is greatly repressed when the homologue is wild type, but less repressed when the reporter is homozygous. Decreased repression is also seen when the homologous telomere is deleted, or when a nonhomologous telomere is disrupted by an insertion into TAS or deleted. We propose that telomeres associate in a ?telocenter?, and that reporter genes placed in the telocenter are repressed. Disruption of the telocenter by insertion of other nontelomeric genes or deletion of one of the components of the telocenter relieves the repression. Sixty-eight transacting modifiers of telomeric repression have been isolated and are being characterized. Similar modifiers of centromeric position effect variegation have been used to identify heterochromatic proteins, but none of these modifiers have an effect on telomeric position effect. This suggests that a new set of telomeric proteins may be identified by the proposed search. - Chromosome Stability, Heterochromatin, Telomere, Drosophila Melanogaster, Gene Expression Regulation

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021054-06
Application #
6289880
Study Section
Special Emphasis Panel (EBMP)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Dronamraju, Raghuvar; Mason, James M (2009) Recognition of double strand breaks by a mutator protein (MU2) in Drosophila melanogaster. PLoS Genet 5:e1000473
Mason, James M; Frydrychova, Radmila Capkova; Biessmann, Harald (2008) Drosophila telomeres: an exception providing new insights. Bioessays 30:25-37
Walter, Marika F; Biessmann, Max R; Benitez, Cecil et al. (2007) Effects of telomere length in Drosophila melanogaster on life span, fecundity, and fertility. Chromosoma 116:41-51
Frydrychova, Radmila Capkova; Biessmann, Harald; Konev, Alexander Y et al. (2007) Transcriptional activity of the telomeric retrotransposon HeT-A in Drosophila melanogaster is stimulated as a consequence of subterminal deficiencies at homologous and nonhomologous telomeres. Mol Cell Biol 27:4991-5001
Biessmann, Harald; Prasad, Sudha; Semeshin, Valery F et al. (2005) Two distinct domains in Drosophila melanogaster telomeres. Genetics 171:1767-77
Biessmann, Harald; Prasad, Sudha; Walter, Marika F et al. (2005) Euchromatic and heterochromatic domains at Drosophila telomeres. Biochem Cell Biol 83:477-85
Mason, James M; Ransom, Joshua; Konev, Alexander Y (2004) A deficiency screen for dominant suppressors of telomeric silencing in Drosophila. Genetics 168:1353-70
Mason, James M; Konev, Alexander Y; Biessmann, Harald (2003) Telomeric position effect in drosophila melanogaster reflects a telomere length control mechanism. Genetica 117:319-25
Mason, James M; Konev, Alexander Y; Golubovsky, Mikhail D et al. (2003) Cis- and trans-acting influences on telomeric position effect in Drosophila melanogaster detected with a subterminal transgene. Genetics 163:917-30
Biessmann, H; Mason, J M (2003) Telomerase-independent mechanisms of telomere elongation. Cell Mol Life Sci 60:2325-33

Showing the most recent 10 out of 12 publications