(A) Schematics of meiotic progression. Expression of non-degradable Δ90 Cyclin B or treatment with ProTAME, an APC/C inhibitor, delays anaphase I onset in the spretus hybrid to at least 4 hours, comparable to the CHPO hybrid. (B) CF-1 x SPRET/EiJ and C57BL/6J x SPRET/EiJ oocytes expressing Major Sat. TALE-mClover and H2B-mCherry were imaged live either shortly before anaphase I (control) or 2–4 hours after spindle migration. Oocytes also expressed Δ90 Cyclin B or were treated with ProTAME or the BUB1 inhibitor BAY-1816032 as indicated. Images are a maximum intensity z-projection of the whole oocyte (top) and an optical slice magnified to show two bivalents (bottom). Solid and dashed white circles indicate the outline of the cell and the spindle, respectively. Graph shows the fraction of bivalents with the larger musculus centromere oriented towards the egg pole; n = 295 bivalents for control, 135 for ProTAME, 134 for Δ90 Cyclin B, and 150 for Δ90 Cyclin B + BAY-1816032. *P < 0.01, indicating significant deviation from 50%. Scale bars, 10 μm. (C) Schematic showing that the direction of centromere drive correlates with MT-destabilizer levels. Musculus centromeres enrich destabilizing activity by increasing kinetochore size, whereas spretus centromeres do so by modulating centromere geometry.