Centrosome-centromere capture range, rather than centrosome arrangement, determines multipolar chromosome segregation pattern after whole-genome duplication

Whole-genome duplication (WGD) leads to chromosome instability through multipolar chromosome segregation driven by supernumerary centrosomes. Two distinct processes, mitotic slippage (MS) and cytokinesis failure (CF), result in differing cell viability post-WGD. MS causes a more skewed homologous chromosome distribution, increasing nullisomic chromosome segregation and poor survival through the first mitosis.

However, the factors behind these route-dependent differences in cell viability are not well understood, especially in relation to the spatial rearrangement of supernumerary centrosomes. Research has revealed significant differences in supernumerary centrosome distribution upon entry into the first mitosis after MS and CF, which are influenced by distinct nuclear geometry.

These differences in centrosome distributions impact kinetochore capture patterning after MS and CF. Nevertheless, their modulations have little effect on the precision of subsequent chromosome segregation. Conversely, artificially extending the centrosome-centromere capture range by depleting the microtubule depolymerizer MCAK significantly suppresses the MS-linked worsening of nullisomic chromosome segregation by equalizing chromosome capture by each supernumerary centrosome.

The findings suggest that the centrosome-centromere capture range, rather than the spatial arrangement of centrosomes, determines the fidelity of chromosome segregation following WGD. This research provides fundamental insights into the mechanisms of atypical cell proliferation following WGD.