A Microtubule-Associated Protein Functions in Preventing Oocytes from Evading the Spindle Assembly Checkpoint

Abstract

Aneuploidy eggs are a common cause of human infertility, spontaneous abortion, or trisomy syndromes. The spindle assembly checkpoint (SAC) plays a crucial role in preventing aneuploidy in oocytes, yet it is unclear if additional mechanisms exist to ensure oocyte adherence to this checkpoint. It is now revealed that the microtubule-associated protein NUSAP can prevent oocytes from evading the SAC and regulate the speed of the cell cycle. Mechanistically, the study identifies NUSAP as a novel stabilizer of the E3 ubiquitin ligase APC/C^CDH1, protecting CDH1 from SCF^BTRC-mediated degradation. Depletion of NUSAP reduces CDH1 protein level, leading to abnormal spindle assembly and chromosome alignment, and disrupting the balance of cell cycle proteins. This misregulated balance causes oocytes to evade the SAC. Consequently, these abnormal oocytes not only fail to arrest at metaphase but also accelerate the cell process, ultimately resulting in the production of aneuploid eggs. Together, the findings not only clarify the existence of mechanisms that ensure oocytes compliance with the spindle assembly checkpoint but also expand the new functions of NUSAP beyond its role as a microtubule- associated protein.