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bioRxiv · 10.1101/2024.08.30.610502

The central spindle drives anaphase chromosome segregation

Chen, G.-Y.·Deng, C.·Chenoweth, D. M.·Lampson, M. A.
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Abstract

Anaphase chromosome segregation depends on forces exerted by spindle microtubules. Current models propose two mechanisms of force generation: kinetochore microtubules (kMTs) depolymerize to pull chromosomes toward the spindle poles (anaphase A), while antiparallel microtubule sliding in the central spindle further separates the chromosomes by elongating the spindle (anaphase B). Experimental evidence in cells supports the sliding mechanism, but contributions of the depolymerization mechanism remain unclear. Here we show that kMT depolymerization limits spindle elongation rather than moving chromosomes apart. We developed a chemical optogenetic approach to recruit a microtubule depolymerase to kinetochores at anaphase onset, thereby increasing the rate of kMT depolymerization without perturbing earlier stages of mitosis. We find that increased depolymerization slows the velocity at which spindle poles move apart without changing kinetochore separation velocities. Our findings support a model in which kinetochores selectively couple to central spindle microtubules parallel to their kMTs, so that antiparallel sliding drives chromosome segregation while kMT depolymerization pulls poles inward.

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Chen, G.-Y., Deng, C., Chenoweth, D. M., Lampson, M. A.. 2024-08-30. The central spindle drives anaphase chromosome segregation. https://doi.org/10.1101/2024.08.30.610502

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