1 The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the Spindle Assembly Checkpoint

Previous studies have established that when maturing mouse oocytes are continually incubated with the Aurora inhibitor ZM447439 meiotic maturation is blocked. Here we observe that by altering the time of addition of the inhibitor, oocyte maturation can actually be accelerated by 1 hour as measured by the timing of polar body extrusion. ZM447439 also had the ability to overcome a Spindle Assembly Checkpoint (SAC) arrest caused by nocodazole and so rescue polar body extrusion. Consistent with the ability of the SAC to inhibit cyclin B1 degradation by blocking activation of the Anaphase-Promoting Complex, we could also observe a rescue in cyclin B1 degradation when ZM447439 was added to nocodazole treated oocytes. The acceleration of the first meiotic division by ZM447439, which has not been achieved previously, and its effects on the SAC are all consistent with the proposed mitotic role of Aurora B in activating the SAC. We hypothesise that Aurora kinase activity controls of the SAC in meiosis I, despite differences to the mitotic cell cycle division in spindle architecture, brought about the meiotic mono-orientation of sister kinetochores