- Mitotic error correction is a fundamental quality‑control mechanism that ensures chromosomes segregate accurately during cell division. Because microtubules attach to kinetochores through a random search‑and‑capture process, cells frequently generate faulty attachments in early mitosis. These include syntelic attachments, where both sister kinetochores connect to the same spindle pole; monotelic attachments, where only one kinetochore is attached; and merotelic attachments, where a single kinetochore binds microtubules from both poles. If these errors are not corrected before anaphase, they lead to chromosome mis‑segregation, aneuploidy and long‑term genomic instability.
- The central regulator of mitotic error correction is Aurora B kinase, the catalytic core of the Chromosomal Passenger Complex. Aurora B is positioned at the inner centromere by INCENP, Borealin and Survivin. From this location, Aurora B senses the mechanical tension generated when sister kinetochores achieve correct bi‑orientation. Incorrect attachments produce little or no tension, allowing Aurora B to phosphorylate outer‑kinetochore substrates such as Ndc80, KNL1 and MCAK. These phosphorylation events weaken microtubule binding, destabilise the faulty attachment and give the cell another opportunity to establish proper bi‑orientation. When tension is high, Aurora B becomes spatially separated from its substrates, stabilising correct attachments and allowing mitosis to progress.
- Mitotic error correction works in close coordination with the spindle assembly checkpoint. When kinetochores lack tension or proper attachment, checkpoint proteins such as Mad2, Bub1 and BubR1 remain active, preventing the anaphase‑promoting complex (APC/C) from triggering sister chromatid separation. Only when all chromosomes achieve correct bi‑orientation does checkpoint signalling silence, allowing separase activation and the onset of anaphase. In this way, error correction repairs faulty attachments while the checkpoint ensures the cell does not proceed prematurely.
- Merotelic attachments represent a special challenge because they generate partial tension and often escape checkpoint detection. Although Aurora B corrects many of these attachments, some persist into anaphase, producing lagging chromosomes, chromatin bridges and micronuclei. These defects are strongly associated with chromosomal instability in cancer. During anaphase and cytokinesis, Aurora B relocates to the spindle midzone and midbody, where it performs late‑stage correction of lagging chromosomes and helps prevent cytokinesis failure.
- Mitotic error correction is frequently compromised in cancer. Tumour cells often show altered Aurora B activity, mis‑localised CPC components and defective kinetochore phosphorylation. These abnormalities allow cells to tolerate high rates of chromosome mis‑segregation while maintaining enough instability to evolve rapidly. Because of this vulnerability, Aurora B inhibitors such as barasertib are being explored as anti‑mitotic cancer therapies that overwhelm tumour cells with uncorrected segregation errors.
- In summary, mitotic error correction is a tension‑sensing, phosphorylation‑driven mechanism that ensures accurate chromosome segregation. Aurora B and the CPC destabilise incorrect attachments, while the spindle assembly checkpoint prevents premature anaphase. Together, they preserve genomic stability and protect cells from aneuploidy.
