Kinetochore life histories reveal an Aurora-B-dependent error correction mechanism in anaphase

Chromosome mis-segregation during mitosis leads to aneuploidy, which is a hallmark of cancer and linked to cancer genome evolution. Errors can manifest as “lagging chromosomes” in anaphase, although their mechanistic origins and likelihood of correction are incompletely understood. Here, we combine lattice light-sheet microscopy, endogenous protein labeling, and computational analysis to define the life history of >104 kinetochores. By defining the “laziness” of kinetochores in anaphase, we reveal that chromosomes are at a considerable risk of mis-segregation. We show that the majority of lazy kinetochores are corrected rapidly in anaphase by Aurora B; if uncorrected, they result in a higher rate of micronuclei formation. Quantitative analyses of the kinetochore life histories reveal a dynamic signature of metaphase kinetochore oscillations that forecasts their anaphase fate. We propose that in diploid human cells chromosome segregation is fundamentally error prone, with an additional layer of anaphase error correction required for stable karyotype propagation. [Display omitted] •Chromosomes are at a considerable and continual risk of mis-segregation•Metaphase dynamics forecast lazy kinetochores and their correction in anaphase•Aurora B spindle midzone gradient enables phosphorylation of kinetochore substrates•Results suggest midzone originated Aurora B activity destabilizes erroneous attachments By tracking human kinetochores from prometaphase to late anaphase, Sen, Harrison et al. reveal that mitotic chromosomes are at a greater risk of mis-segregation than previously appreciated. They uncover an anaphase error correction mechanism that combats this mis-segregation and show that kinetochore behavior before anaphase can predict future segregation outcome.