Tension-Induced Error Correction and Not Kinetochore Attachment Status Activates the SAC in an Aurora-B/C-Dependent Manner in Oocytes
Abstract
Cell division should only proceed with the proper partitioning of genetic material when paired chromosomes—bivalents in meiosis I or sister chromatids in mitosis and meiosis II—are correctly attached to the bipolar spindle under tension. To ensure this, the spindle assembly checkpoint (SAC) monitors for unattached kinetochores, delaying anaphase onset until stable attachments are established. Additionally, microtubules are stabilized when properly attached and under tension. In mitosis, improper attachments lacking tension activate the error correction pathway, which relies on Aurora B kinase-mediated phosphorylation to detach microtubules, thereby triggering the SAC.
Meiotic divisions in mammalian oocytes are particularly error-prone, posing significant risks to fertility and offspring health. In meiosis I, correct chromosome attachment results in stretched bivalents but does not generate tension between sister kinetochores, which co-orient. This study investigates whether reduced spindle tension on bioriented bivalents activates the error correction mechanism and, consequently, the SAC. Treatment of late prometaphase I oocytes with an Eg5 kinesin inhibitor Litronesib disrupts spindle tension without affecting attachments, as demonstrated through an optimized confocal imaging protocol. Following Eg5 inhibition, bivalents remain properly aligned but exhibit reduced stretching, leading to Aurora-B/C-dependent error correction and subsequent microtubule detachment. This detachment activates the SAC; however, crucially, SAC activation in oocytes occurs independently of Aurora B/C kinase activity.