Regulation of cell cycle and DNA damage response in mouse oocytes.

• Main Author: Mayer, Alexandra
• Other Authors: Šolc, Petr
• Format: Doctoral Thesis
• Language: Czech
• Published: 2015
• Online Access: http://www.nusl.cz/ntk/nusl-350100

A specific feature of mammalian oocytes is a long prophase I arrest, which can be maintained for many years in humans. The oocytes must ensure robust mechanisms, which can keep them in prophase I, but effectively trigger meiotic resumption when required. Consequently, throughout the maturation of an oocyte, non-erroneous chromosome segregation is a prerequisite for the generation of healthy offspring. In this study we aimed to investigate the new roles of Aurora A (AURKA) and polo-like kinase 1 (PLK1) in the regulation of the cell cycle progression. For this purpose, we used transgenic mice that specifically overexpress wild type (WT-) or kinase-dead (KD-) AURKA in oocytes only, and to study PLK1 we treated oocytes with BI2536, a small molecule inhibitor known to specifically inhibit PLK1 in somatic cells. Our data show, that both AURKA and PLK1 are not essential for meiotic resumption, however they participate in this process. Active AURKA regualtes the increase in microtubule organizing centers (MTOC) in prophase I, which is the first visible marker of resumption of meiosis in oocytes. AURKA activation is biphasic, and the initial increase in MTOC is transient, while full AURKA activation needed for the stability of MTOC requires the activity of Cyclin-dependent kinase 1 (CDK1). We show that PLK1...