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Polynucleotides with insulating properties allowing protection of the expression of a transgene from adjacent cis elements in higher eukaryotic cells. In particular, these polynucleotides can be used for transgenesis, gene therapy and the production of recombinant proteins.; L'invention porte sur des polynucléotides présentant des propriétés isolantes permettant la protection de l'expression d'un transgène à partir d'éléments cis adjacents dans des cellules eucaryotes supérieures. En particulier, ces polynucléotides peuvent être utilisés pour la transgenèse, la thérapie génique et la production de protéines recombinantes.

The telomeres protect the end of chromosomes from being recognized and processed as an accidental double stranded break. In human somatic cells, telomeres shorten progressively with every round of DNA replication, leading to dysfunctional telomeres that trigger cellular senescence or apoptosis depending on the cell type. This telomere erosion appears to play a role in cell renewal, ageing and cancer. Two recent studies demonstrated in mouse that eroded telomeres in cancer cells blocked for apoptosis limit cancer formation by triggering senescence. These results suggest that provoking senescence may provide a way to cure cancer and point to new therapeutical strategies targeting specific telomeric functions. Nevertheless, an important question remains unanswered: does replicative senescence limit tumor formation in human?

Telomeres are nucleoprotein complexes that cap the end of eukaryotic chromosomes. They are essential for the functions and the stability of the genomes. There is now compelling evidences that telomerase, the enzyme that adds telomeric DNA repeats to chromosome end, is an important player in oncogenesis. The absence of telomerase in somatic tissues is thought to promote genome instability at initial stages of oncogenesis, favoring the emergence of cancer-associated chromosomal abnormalities \; restablishment of telomerase activity is expected afterwards if long term cell cycling is to occur. In addition to telomerase, various factors control the structure and function of telomeres, suggesting that additional telomeric components play important roles during oncogenesis.

Les télomères sont des structures nucléoprotéiques, coiffant les chromosomes eucaryotes, qui sont essentielles pour les fonctions et la stabilité du génome. Il est maintenant bien établi que la télomérase, l’enzyme qui ajoute les répétitions d’ADN télomérique aux extrémités de chromosome, est un acteur clé de l’oncogenèse. D’une part, l’absence de télomérase dans les tissus somatiques pourrait permettre la mise en place de certaines étapes précoces du déclenchement des cancers en favorisant l’instabilité génétique. D’autre part, l’activation de la télomérase dans les cellules cancéreuses est requise pour permettre la croissance à long terme des cellules transformées. Outre la télomérase, de nombreux facteurs contrôlent la structure et la fonction des télomères, suggérant qu’ils puissent aussi participer à l’oncogenèse., Telomeres are nucleoprotein complexes that cap the end of eukaryotic chromosomes. They are essential for the functions and the stability of the genomes. There is now compelling evidences that telomerase, the enzyme that adds telomeric DNA repeats to chromosome end, is an important player in oncogenesis. The absence of telomerase in somatic tissues is thought to promote genome instability at initial stages of oncogenesis, favoring the emergence of cancer-associated chromosomal abnormalities ; restablishment of telomerase activity is expected afterwards if long term cell cycling is to occur. In addition to telomerase, various factors control the structure and function of telomeres, suggesting that additional telomeric components play important roles during oncogenesis.

Telomeres are nucleoprotein complexes that cap the end of eukaryotic chromosomes. They are essential for the functions and the stability of the genomes. In the absence of telomerase, the enzyme that adds telomeric DNA repeats to chromosome ends, telomeres shorten with cell division, a process thought to contribute to cell senescence. Reciprocally, telomere stabilization in immortalized cells, that usually appears concomitant with detection of telomerase activity, suggests that telomerase is essential for unlimited cell proliferation. Sequential modifications in the function of telomeres play antagonistic functions as far as tumorigenesis is concerned. Telomere dysfunction is thought to promote genome instability at initial stages, favoring the emergence of cancer-associated chromosomal abnormalities; reestablishment of telomere maintenance is expected afterwards if efficient cell cycling is to occur.