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Theses

Etude des fonctions mitotiques du domaine amino-terminal de CENP-A

Abstract : The histone variant CENP-A is the epigenetic factor responsible for centromere deter- mination. It allows the recruitment of a handful of centromeric proteins, and thus acts as the primary foundation for the kinetochore. It comprises an unstructured amino-terminal domain to which no precise function has yet been assigned, although it is established in some species that the mere presence of that domain is required for proper centromere func- tion and thus successful completion of mitosis. We have established several human cell lines stably expressing GFP-tagged CENP-A constructs, allowing us to perform pseudoge- netic experiments by siRNA-mediated silencing of the endogenous CENP-A. Our results show a dramatic increase of mitotic defects and plurinuclear cells when cells express only the globular domain of CENP-A; this is in accordance with the litterature and confirms the importance of the amino-terminal tail. More importantly, a similar increase of mitotic defects is observed when cells express a full-length, but non-phosphatable, CENP-A. Our results show the involvement of the phosphatable serine 7 of CENP-A in the successful completion of mitosis, and may suggest that the role of the whole amino-terminal tail of CENP-A could be reduced to this single phosphorylation event.
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Damien Goutte-Gattat. Etude des fonctions mitotiques du domaine amino-terminal de CENP-A. Autre [q-bio.OT]. Université de Grenoble, 2011. Français. ⟨NNT : 2011GRENV079⟩. ⟨tel-00716378⟩

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