An anaphase surveillance mechanism prevents micronuclei formation from mitotic errors

Abstract

Micronuclei are a hallmark of cancer and other human disorders and have recently been implicated in chromothripsis, a series of massive genomic rearrangements that may drive tumor evolution and progression. Here we show that Aurora B kinase mediates a surveillance mechanism that integrates error correction during anaphase with spatial control of nuclear envelope reformation to protect against micronuclei formation during human cell division. Using high-resolution live-cell imaging of human cancer and non-cancer cells we found that anaphase lagging chromosomes are often transient and rarely formed micronuclei. This strong bias against micronuclei formation relied on a midzone-based Aurora B phosphorylation gradient that assisted the mechanical transduction of spindle forces at the kinetochore-microtubule interface required for anaphase error correction, while delaying nuclear envelope reformation on lagging chromosomes, independently of microtubules. Our results uncover a new layer of protection against genomic instability and provide a strategy for the rational design of micronuclei-targeting therapies.