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Non-canonical function of spindle assembly checkpoint proteins after APC activation reduces aneuploidy in mouse

Simon I R Lane1, Keith T Jones1

  • 11] Centre for Biological Sciences, Faculty and Natural and Environmental Sciences, University of Southampton, Southampton SO17 1BJ, UK [2] School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia.

Nature Communications
|March 19, 2014
PubMed

Insights

Oocytes maintain sub-maximal spindle assembly checkpoint (SAC) activity during meiosis I. This allows more time for correcting chromosome attachment errors, significantly reducing aneuploidy risk in eggs.

Area of Science:

  • Cell Biology
  • Genetics
  • Developmental Biology

Background:

  • The spindle assembly checkpoint (SAC) is crucial for preventing aneuploidy.
  • Oocytes are particularly prone to chromosome mis-segregation during meiosis I (MI).
  • The anaphase-promoting complex (APC) regulates anaphase onset and chromosome attachment.

Purpose of the Study:

  • To investigate APC activity in oocytes during MI.
  • To determine the interplay between SAC proteins and APC in oocytes.
  • To understand how this interaction impacts aneuploidy rates.

Main Methods:

  • Measurement of cyclin B1-GFP degradation to assess APC activity.
  • Inhibition of SAC proteins during oocyte meiosis I.
  • Quantification of aneuploidy rates in resulting eggs.

Main Results:

  • Oocytes exhibit sub-maximal APC activity during MI.
  • Inhibiting SAC proteins during active APC periods accelerated cyclin B1 degradation by twofold and shortened MI by 2 hours.
  • Inhibiting the SAC component Mps1 during active APC increased aneuploidy rates by up to 30%.

Conclusions:

  • SAC proteins and APC activity coexist and function concurrently in oocytes.
  • This concurrent activity is vital for reducing aneuploidy by extending MI.
  • Extended MI likely provides essential time for correcting erroneous microtubule attachments.

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