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Use of Time-Lapse Microscopy and Stage-Specific Nuclear Depletion of Proteins to Study Meiosis in S. cerevisiae
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Use of Time-Lapse Microscopy and Stage-Specific Nuclear Depletion of Proteins to Study Meiosis in S. cerevisiae

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A mutual inhibition between APC/C and its substrate Mes1 required for meiotic progression in fission yeast

Yuu Kimata1, Michelle Trickey, Daisuke Izawa

  • 1Cell Cycle Control Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, United Kingdom.

Developmental Cell
|March 12, 2008
PubMed

Insights

Fission yeast Mes1 acts as both a substrate and inhibitor of the anaphase-promoting complex/cyclosome (APC/C), enabling its autoregulation during meiosis. This crucial feedback loop fine-tunes APC/C activity for proper meiotic progression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The anaphase-promoting complex/cyclosome (APC/C) is a critical E3 ubiquitin ligase regulating the cell cycle.
  • Its specific role in meiotic regulation remains largely unexplored.

Purpose of the Study:

  • To investigate the meiotic regulation of the APC/C in fission yeast.
  • To elucidate the function of the Mes1 protein in APC/C activity during meiosis.

Main Methods:

  • Investigated Mes1 as an APC/C substrate and inhibitor.
  • Utilized functional destruction box (D box) and KEN box assays.
  • Examined Mes1 binding to Fizzy family APC/C activators.
  • Analyzed the effects of non-ubiquitylatable Mes1 mutants.

Main Results:

  • Mes1 is a substrate and inhibitor of the APC/C, requiring D box and KEN box motifs.
  • Mes1 directly binds to the WD40 domain of Fizzy/Cdc20.
  • Non-ubiquitylatable Mes1 causes metaphase I arrest with high APC/C substrate levels.
  • Mes1 ubiquitylation is essential for partial cyclin B degradation and progression through meiosis I.

Conclusions:

  • Mes1's dual role as substrate and inhibitor allows for autoregulation of the APC/C in meiosis.
  • Fine-tuning APC/C activity via Mes1 is critical for accurate meiotic transitions.
  • A stabilized APC/C-Fizzy/Cdc20-Mes1 complex is regulated by Mes1 ubiquitylation.

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