Data for "Spindle checkpoint can secure additional cheating time for selfish expanded centromeres".

Microscopy images analyzed in the Figures and Supplemental Figures in Walton et al "Spindle checkpoint can secure additional cheating time for selfish expanded centromeres".

Summary:

Expanded centromeric satellite repeats can violate Mendel’s Law of Segregation by preferentially segregating to the egg. In mice, these selfish centromeres enrich microtubule-destabilizers at pericentromeres to detach from the spindle and flip towards the egg side of the meiotic spindle, thereby achieving preferential segregation. However, despite consistent enrichment of destabilizers upon centromere expansion, such enrichment alone is insufficient to drive preferential retention of expanded centromeres, suggesting a missing component in understanding their non-Mendelian segregation. Here we propose that prolonged spindle checkpoint activation is crucial for expanded centromeres to cheat the segregation process by providing sufficient time for them to flip towards the egg side. By experimentally manipulating kinetochore size in a species-specific manner, we found that assembling larger kinetochores triggers robust spindle checkpoint activation, leading to anaphase delay and preferential retention of expanded centromeres in the egg. Comparisons across multiple hybrid mouse models revealed that centromeric satellite asymmetry does not consistently lead to kinetochore asymmetry and anaphase delay, explaining why satellite asymmetry does not always result in preferential retention of larger centromeres. Altogether, this work highlights the significance of checkpoint activation in exploiting the inherent asymmetry in female meiosis and the distinct responses of kinetochore proteins and microtubule-destabilizers to centromere expansion.