Regulatory Mechanisms of Meiosis in Vertebrate Oocytes

• Applicant: Professor Dr. Thomas Mayer
• Subject Area: Cell Biology
• Term: from 2009 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 160225854

Meiosis involves two consecutive rounds of nuclear divisions without intervening DNA-synthesis re-sulting in the formation of haploid gametes. Errors in this pathway can result in severe embryonic defects. The overarching goal of this project is to better understand the mechanisms regulating meiotic progression. These studies focus on XErp1/Emi2, an inhibitor of the ubiquitin-ligase anaphase-promoting complex/cyclosome (APC/C), as well as on the ubiquitin-ligase complex SCF (Skp1/Cul-1/F-box protein). In particular, we will explore i) the function of XErp1 as an F-box protein in meiosis, ii) the role of SCFs in regulating meiotic maturation, and iii) the mechanism of XErp1-mediated APC/C inhibition. For these studies, we will perform depletion-rescue experiments in Xenopus laevis oocytes, biochemical studies in meiotic extracts and reconstituted in vitro systems, and quantitative mass spectrometry analyses. The proposed studies will contribute to a better understanding of how selective protein destruction by ubiquitin-ligases can control protein activities in a timely switch-like manner to ensure that onset of and progression through meiotic divisions occur in an irreversible and unidirectional manner.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1384: Mechanisms of Genome Haploidisation