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1.
Mol Cell Biol ; 27(13): 4991-5001, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17470550

ABSTRACT

Drosophila melanogaster telomeres have two DNA domains: a terminal array of retrotransposons and a subterminal repetitive telomere-associated sequence (TAS), a source of telomere position effect (TPE). We reported previously that deletion of the 2L TAS array leads to dominant suppression of TPE by stimulating in trans expression of a telomeric transgene. Here, we compared the transcript activities of a w transgene inserted between the retrotransposon and TAS arrays at the 2L telomere in genotypes with different lengths of the 2L TAS. In contrast to individuals bearing a wild-type 2L homologue, flies with a TAS deficiency showed a significant increase in the level of telomeric w transcript during development, especially in pupae. Moreover, we identified a read-through w transcript initiated from a retrotransposon promoter in the terminal array. Read-through transcript levels also significantly increased with the presence of a 2L TAS deficiency in trans, indicating a stimulating force of the TAS deficiency on retrotransposon promoter activity. The read-through transcript contributes to total w transcript, although most w transcript originates at the w promoter. While silencing of transgenes in nonhomologous telomeres is suppressed by 2L TAS deficiencies, suggesting a global effect, the overall level of HeT-A transcripts is not increased under similar conditions.


Subject(s)
Drosophila melanogaster/genetics , Retroelements/genetics , Telomere/genetics , Transcription, Genetic , Animals , Base Sequence , Gene Expression Regulation , Molecular Sequence Data , Promoter Regions, Genetic/genetics , RNA, Messenger/genetics , Sequence Homology , Transgenes
2.
Exp Gerontol ; 41(9): 819-27, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16905287

ABSTRACT

Recent studies suggest that downregulation of tumor suppressor genes might not only favor cancer development but also postpone organisms' aging and increase longevity. However, there is lack of population-based studies directly supporting this idea. We studied the lgl lethal alleles which are widespread in natural Drosophila populations. We demonstrate, for the first time, that animals heterozygous on the loss-of-function lgl tumor suppressor gene display a clear pre-adult viability advantage under stressful conditions (high 29 degrees C and low 16 degrees C temperatures). We found also the survival and longevity advantage effect of the lgl loss-of-function in the temperature stress conditions. The main features of this longevity influence are following. First, the lgl-dependent life span increase is sex-dependent; in all experimental combinations males are more sensitive than females of relevant genotypes. Second, the effect is stronger under the life-shortening temperature stress, 29 degrees C, where the hormesis was demonstrated. Third, the favoring effect of reduced dosage of tumor suppressor displays clearly in old but not young animals, delaying aging. Forth, the maternal or epigenetic inheritance of thermotolerance from mother to offspring appears to strengthen the observed longevity effects. One possible explanation of this stress-adaptive effect of reduced tumor suppressor dose might be a better resistance of Drosophila post-mitotic cells to a stress-associated apoptosis at old ages.


Subject(s)
Drosophila Proteins/genetics , Drosophila/genetics , Longevity/genetics , Tumor Suppressor Proteins/genetics , Alleles , Animals , Drosophila/growth & development , Epigenesis, Genetic/genetics , Female , Genotype , Heterozygote , Male , Mutation , Sex Factors , Stress, Physiological/genetics , Temperature
3.
Genetics ; 163(3): 917-30, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12663532

ABSTRACT

One model of telomeric position effect (TPE) in Drosophila melanogaster proposes that reporter genes in the vicinity of telomeres are repressed by subterminal telomere-associated sequences (TAS) and that variegation of these genes is the result of competition between the repressive effects of TAS and the stimulating effects of promoters in the terminal HeT-A transposon array. The data presented here support this model, but also suggest that TPE is more complex. Activity of a telomeric white reporter gene increases in response to deletion of some or all of the TAS on the homolog. Only transgenes next to fairly long HeT-A arrays respond to this trans-interaction. HeT-A arrays of 6-18 kb respond by increasing the number of dark spots on the eye, while longer arrays increase the background eye color or increase the number of spots sufficiently to cause them to merge. Thus, expression of a subtelomeric reporter gene is influenced by the telomere structure in cis and trans. We propose that the forces involved in telomere length regulation in Drosophila are the underlying forces that manifest themselves as TPE. In the wild-type telomere TAS may play an important role in controlling telomere elongation by repressing HeT-A promoter activity. Modulation of this repression by the homolog may thus regulate telomere elongation.


Subject(s)
Drosophila melanogaster/genetics , Telomere/genetics , Animals , Animals, Genetically Modified , Base Sequence , Eye Color/genetics , Genes, Reporter , Models, Genetic , Molecular Sequence Data , Polymerase Chain Reaction/methods
4.
Twin Res ; 5(4): 294-307, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12217237

ABSTRACT

Paternal influence on twinning was investigated through a study of all the state and church records of Scotland for the period 1800-2000 (nine generations) in relation to one Scottish patronymic - in total 50,000 births. All recorded twins born with the chosen patronymic were identified and their whole paternal ascent and descent on the male line were charted for twins. There were established three pedigrees A, B and C manifesting clear paternal twinning hereditary transmission. Detailed familial reproduction patterns were traced for pedigree A, including phenotypic identification of twin zygosity in relation to seven same sexed pairs of twins in the pedigree and one same sexed pair out of dizygotic triplets. It is the most comprehensive description to date of such a kind of twin familial trait. The data presented show (i) the unique feature of clear direct paternal influence on twinning in three families; (ii) paternal factor(s) determination in both DZ and MZ twinning; and (iii) a definite association of twinning tendency with a partial male infertility, which corresponds to the prediction of the Infertility/Twinning Paternally Dependent syndrome hypothesis. The hypothesis of a founder effect explaining the similarity of A, B, C families and the possible localisation of the paternally dependent twinning factor on the Y-chromosome are currently under molecular investigation.


Subject(s)
Paternity , Twins/genetics , Adult , Female , Humans , Infertility, Male/genetics , Male , Maternal Age , Pedigree , Scotland , Twins, Dizygotic/genetics , Twins, Monozygotic/genetics
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