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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021054-08
Application #
6508836
Study Section
(LMG)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2001
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
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