Determinants of robustness in spindle assembly checkpoint signalling

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• The spindle assembly checkpoint (SAC) is crucial for maintaining genome integrity during cell division.
• Understanding the robustness and underlying mechanisms of the SAC against perturbations is essential.

Purpose of the Study:

• To investigate the robustness of the spindle assembly checkpoint signaling pathway.
• To identify mechanisms that ensure reliable SAC function despite potential fluctuations.

Main Methods:

• Modulating checkpoint protein abundance and nutrient conditions in fission yeast (Schizoscscharomyces pombe).
• Quantifying protein abundance in single cells to assess variability (noise).
• Analyzing checkpoint-mediated stoichiometric inhibition of the anaphase activator Cdc20 (Slp1).

Main Results:

• A reduction of just 20% in core checkpoint proteins significantly impairs SAC signaling, indicating fragility.
• Minimal variability (low noise) in critical protein abundance explains the checkpoint's normal reliability.
• Checkpoint-mediated stoichiometric inhibition of Cdc20/Slp1 accounts for tolerance to small protein fluctuations.

Conclusions:

• Low gene expression noise is a key factor for reliable spindle assembly checkpoint signaling.
• The SAC's robustness relies on both low intrinsic noise and specific regulatory mechanisms like stoichiometric inhibition.