One possible explanation is that persistent SAC signaling could lead to cohesion fatigue, where the cohesin complexes that hold sister chromatids together become exhausted over time, resulting in aberrant sister chromatid segregation.226,227 Together, while the SAC plays a vital role in ensuring accurate chromosome segregation during mitosis, both its defect and hyperactivation can paradoxically lead to CIN. This evidence concerns the gene ADCY10 and cervical squamous intraepithelial neoplasia.