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Aurora kinase signaling during mammalian oocyte meiosis
Komrsková, Anna ; Drutovič, David (advisor) ; Petr, Jaroslav (referee)
Mammalian oocytes, especially human oocytes, are prone to defective chromosome segregation and are prone to aneuploidies, most commonly in the first meiotic division. Due to these defects, aneuploid embryos are formed after fertilization, resulting in numerous birth defects or infertility. The spindle formation in the first meiotic division in mammalian ooctes is a critical moment for preserving genome integrity. In mammalian oocytes, the spindle assembly is regulated via acentriolar microtubule-organizing centers and chromatine itself, through the activity of Aurora kinases and Ran-GTP gradient. Apart from the Aurora kinase family, other kinases regulate spindle formation, like Polo-like kinase 1 (PLK1). This thesis focused on potential cooperation between Aurora kinases and PLK1 or Ran-GTP. Our results show that the levels of phosphorylated Aurora kinase A (AURKA), but not levels of phosphorylated Aurora kinase B or Aurora kinase C, decrease after pharmacological inhibiton of PLK1. Levels of phosphorylated Aurora kinases do not change after pharmacological inhibition of Ran-GTP signaling. Using live-cell microscopy we showed that overexpression of PLK1 can rescue the phenotype observed in Aurka depleted oocytes. Next, we found that at least one of the signal pathways at chromosomes is necessary...
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The role of protein kinases in spindle formation and chromosome segregation during mammalian oocyte meiosis
Komrsková, Anna ; Drutovič, David (advisor) ; Libusová, Lenka (referee)
Correctly assembled spindle during the first meiotic division is crucial for proper chromosome segregation. Protein kinases from Aurora kinase and Polo-like kinase families are an essential part of mechanisms that affect spindle assembly and take part in chromosome segregation. These kinases play a very specific role in these processes both individually and in cooperation. A defective spindle assembly is often followed by incorrect chromosome segregation, that can lead to aneuploidy. Some aneuploidies cause infertility, others lead to birth defects like Down's syndrome. Human oocyte meiosis is more sensitive to errors in chromosome segregation than mitosis, meiosis in human sperm or meiosis in female gametes in other organisms. This tendency makes the research of Aurora kinases and Polo-like kinases very appealing and eventually rewarding in the context of human reproduction. Keywords Meiosis, oocytes, spindle, microtubule-organising centers, protein kinases, Aurora kinases, Polo-like kinases
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