2. Academic Validation
  3. ProTAME Arrest in Mammalian Oocytes and Embryos Does Not Require Spindle Assembly Checkpoint Activity

ProTAME Arrest in Mammalian Oocytes and Embryos Does Not Require Spindle Assembly Checkpoint Activity

  • Int J Mol Sci. 2019 Sep 13;20(18):4537. doi: 10.3390/ijms20184537.
Lenka Radonova 1,  Tereza Svobodova 2,  Michal Skultety 3 4,  Ondrej Mrkva 5,  Lenka Libichova 6,  Paula Stein 7,  Martin Anger 8
Affiliations

Affiliations

  • 1 Central European Institute of Technology, Department of Genetics and Reproduction, Veterinary Research Institute, 621 00 Brno, Czech Republic. radonova@vri.cz.
  • 2 Central European Institute of Technology, Department of Genetics and Reproduction, Veterinary Research Institute, 621 00 Brno, Czech Republic. svobodova@vri.cz.
  • 3 Central European Institute of Technology, Department of Genetics and Reproduction, Veterinary Research Institute, 621 00 Brno, Czech Republic. skultety@vri.cz.
  • 4 Cellular Imaging Core Facility, Central European Institute CEITEC Masaryk University, 624 00 Brno, Czech Republic. skultety@vri.cz.
  • 5 Central European Institute of Technology, Department of Genetics and Reproduction, Veterinary Research Institute, 621 00 Brno, Czech Republic. mrkva@vri.cz.
  • 6 Central European Institute of Technology, Department of Genetics and Reproduction, Veterinary Research Institute, 621 00 Brno, Czech Republic. lenlibichova@gmail.com.
  • 7 National Institute of Environmental Health Sciences, NIH, Durham, NC 27709, USA. paula.stein@nih.gov.
  • 8 Central European Institute of Technology, Department of Genetics and Reproduction, Veterinary Research Institute, 621 00 Brno, Czech Republic. anger@vri.cz.
PMID: 31540287 DOI: 10.3390/ijms20184537
Abstract

In both mitosis and meiosis, metaphase to anaphase transition requires the activity of a ubiquitin Ligase known as anaphase promoting complex/cyclosome (APC/C). The activation of APC/C in metaphase is under the control of the checkpoint mechanism, called the spindle assembly checkpoint (SAC), which monitors the correct attachment of all kinetochores to the spindle. It has been shown previously in somatic cells that exposure to a small molecule inhibitor, prodrug tosyl-l-arginine methyl ester (proTAME), resulted in cell cycle arrest in metaphase, with low APC/C activity. Interestingly, some reports have also suggested that the activity of SAC is required for this arrest. We focused on the characterization of proTAME inhibition of cell cycle progression in mammalian oocytes and embryos. Our results show that mammalian oocytes and early cleavage embryos show dose-dependent metaphase arrest after exposure to proTAME. However, in comparison to the somatic cells, we show here that the proTAME-induced arrest in these cells does not require SAC activity. Our results revealed important differences between mammalian oocytes and early embryos and somatic cells in their requirements of SAC for APC/C inhibition. In comparison to the somatic cells, oocytes and embryos show much higher frequency of aneuploidy. Our results are therefore important for understanding chromosome segregation control mechanisms, which might contribute to the premature termination of development or severe developmental and mental disorders of newborns.

Keywords

anaphase promoting complex; cell cycle; meiosis; oocytes; proTAME; spindle assembly checkpoint.

Figures
Products
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    Product Name
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    Target
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  • HY-124955
    99.94%, APC抑制剂
    APC
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