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Chemical and genetic perturbations of centrosomes and their consequences on the mitotic spindle functions

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Defense Thèse de doctorat : Univ. Genève, 2020 - Sc. Vie 62 - 2020/04/24
Abstract Eukaryotic cells rely on mitosis to divide into two genetically identical cells. One of the main actors ensuring chromosome segregation is the centrosome, the major microtubule organising centre of animal cells. Centrosome duplicates only once per cell cycle, so that mitosis starts with two centrosomes differing in age. Kinetochore-microtubule attachments emanating from the old centrosome are more stable, which causes a bias in chromosomes fate when sister-chromatids are not separated properly. In the first part of my PhD, I used gene depletion and kinase inhibition to identify centrosomal proteins involved in this differential property of centrosomes. In a second part, I studied supernumerary centrosomes, which are commonly found in cancer cells and are linked to poor prognosis. To survive, cancer cells cluster their extra centrosomes and divide with a pseudo-bipolar spindle. I characterized the mechanism of a clinically relevant drug combination which displayed an anti-centrosome clustering effect in renal cancer cells and melanoma.
Keywords CentrosomeCentrobinPLK1Centrosome clusteringDrug combination
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URN: urn:nbn:ch:unige-1385424
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Thesis (13.7 MB) - private document Private access (until 2021-07-08)
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Research group Groupe Meraldi Patrick (physiologie cellulaire et métabolisme) (922)
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LE ROUX-BOURDIEU, Morgan. Chemical and genetic perturbations of centrosomes and their consequences on the mitotic spindle functions. Université de Genève. Thèse, 2020. doi: 10.13097/archive-ouverte/unige:138542 https://archive-ouverte.unige.ch/unige:138542

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Deposited on : 2020-07-22

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