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Financement de l’UE (1 500 000 €) : Étude de la fonction des télomères dans les cellules germinales, pertinente pour la régulation de la recombinaison homologue et du maintien de la longueur des … Hor14/11/2018 Programme de recherche et d'innovation de l'UE « Horizon »
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Étude de la fonction des télomères dans les cellules germinales, pertinente pour la régulation de la recombinaison homologue et du maintien de la longueur des télomères à travers les générations
The length of telomeric DNA is a critical determinant factor for aging and cancer development. In germ cells, the activation of a telomerase-dependent telomere-lengthening pathway is thought to be important in order to maintain telomeric DNA across generations, but the molecular mechanisms involved in this pathway, i.e: how and when telomerase is activated in germ cells, are largely unknown. A DNA-binding protein complex called shelterin constitutively binds telomeric DNA. However, my recent studies have suggested that a multi-subunit DNA-binding complex, TERB1-TERB2-MAJIN, takes over telomeric DNA from shelterin in mammalian germ cells in order to facilitate homologous recombination. These findings represent a hitherto unknown molecular mechanism at work on the telomeres in germ cells. In this project, I hypothesize that the drastic reformation of telomere-binding complexes in germ cells contributes also to the telomere-lengthening pathway. The aim of this project is to test this hypothesis in order to reveal the mechanism underlying the transgenerational inheritance of telomeric DNA throughout meiosis. This work is divided into three work packages. WP1: to determine the molecular rearrangements that take place at telomeres during meiosis. WP2: to determine how and when telomeres are lengthened during germ cell production. WP3: to determine how meiotic recombination is achieved. The proposed project will reveal molecular mechanisms underlying the transgenerational inheritance of genetic information after meiosis, and this will increase our understanding of the etiology of numerous human diseases caused by meiotic errors, such as congenital birth defects and aneuploidy. Further, because the misregulation of telomerase is a leading cause of cancer development, the identification of telomerase-activating mechanisms in germ cells will have multidiscipline impacts in both cancer and reproductive biology fields and will be useful for developing novel cancer therapies.
| Goeteborgs Universitet | 1 500 000 € |
https://cordis.europa.eu/project/id/801659
Cette annonce se réfère à une date antérieure et ne reflète pas nécessairement l’état actuel. L’état actuel est présenté à la page suivante : Göteborgs universitet Statliga enheter, Göteborg, Suède.