Alghassimou Diallo

Identification of a new function of Protein kinase Aurora-A

Abstract:
Protein kinases "Aurora " are the key regulators of the cell cycle. While the activity of Aurora-A is required at the beginning of mitosis, Aurora-B and -C are required for the end of mitosis. Any disruption of their activity can lead to process tumorisation. Specifically, Aurora-A acts as both oncogene and tumor suppressor. Therefore, knowledge of the role of Aurora-A is essential for cell cycle. However, few studies have explored so far, the role of Aurora-A in the late stages of mitosis. In fact, inhibition of Aurora-A leads to cell cycle arrest making it impossible to see what happens beyond the transition metaphase / anaphase. However, by combining chemical genetics couple and specific inhibitor, I have identified a new function of Aurora-A kinase -related checkpoint (SAC). Indeed, my results show that inhibition of the activity of Aurora-A induces a congression defect and the mitotic index decrease. This paradoxical result suggests a defect in the SAC. So I have shown that this inhibition was beyond the SAC disrupting kinetochore localization of Mad2 and BubR1. However, my attempt to rescue the phenotype of the SAC by the S19D-P150Glued mutant failed despite the fact that S19A-P150Glued mutant behaved like a true negative dominant. Finally, I have shown that the activity of Aurora-A is required to maintain the active SAC during prometaphase.

Financial Support :
Government of Republic of Guinea

Committee:  : December 18th 2013
Régis Giet
Katja Wassmann
Sandrine Ruchaud
Claude Prigent (PhD Director)

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