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APC(FZR1) prevents nondisjunction in mouse oocytes by controlling meiotic spindle assembly timing

Janet E Holt1, Simon I R Lane, Phoebe Jennings

  • 1School of Biomedical Sciences, University of Newcastle, Callaghan, NSW 2308, Australia. Janet.holt@newcastle.edu.au

Molecular Biology of the Cell
|August 25, 2012
PubMed

Insights

FZR1 loss accelerates meiosis I in mouse oocytes by enabling faster spindle assembly and earlier checkpoint satisfaction. This leads to chromosome nondisjunction, highlighting FZR1

Area of Science:

  • Cell Biology
  • Genetics
  • Reproductive Biology

Background:

  • FZR1 (also known as Cdh1) is an activator of the anaphase-promoting complex (APC/C), crucial for cell cycle progression, genome integrity, and preventing meiotic resumption.
  • Previous research established FZR1's role in mitotic exit and G1 phase, and its function in suppressing meiotic resumption, which is equivalent to the G2/M transition.

Purpose of the Study:

  • To investigate the role of FZR1 in mouse oocyte meiosis I, specifically its impact on spindle assembly, checkpoint satisfaction, and chromosome segregation.
  • To determine if FZR1 deficiency affects spindle assembly checkpoint (SAC) functionality or timing.

Main Methods:

  • Analysis of mouse oocytes lacking FZR1.
  • Assessment of meiotic progression, spindle assembly, SAC satisfaction, and chromosome nondisjunction rates.
  • Evaluation of APC(CDC20) activity and kinetochore-bound MAD2 localization.

Main Results:

  • Oocytes lacking FZR1 exhibited accelerated meiosis I progression by approximately 1 hour due to earlier spindle assembly checkpoint (SAC) satisfaction and APC(CDC20) activation.
  • FZR1 deficiency did not impair SAC function but led to faster bipolar meiotic spindle assembly, premature bivalent attachment, and reduced kinetochore-bound MAD2.
  • Poor bivalent congress in FZR1-deficient oocytes resulted in significant chromosome nondisjunction rates (25%).

Conclusions:

  • In mouse oocytes, FZR1 is a key regulator controlling the timing of bipolar spindle assembly during prometaphase.
  • By regulating spindle assembly timing, FZR1 influences the timing of SAC satisfaction and APC(CDC20) activity.
  • FZR1's role in controlling spindle assembly is essential for preventing chromosome nondisjunction during meiosis I.

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