# Mitosis & the spindle assembly checkpoint

Source: https://onco.cc/pathways/mitotic-spindle-checkpoint/  
OnCo record `mitotic-spindle-checkpoint` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

When a cell divides, a scaffold of microtubules (the spindle) pulls one copy of each chromosome to each side. A checkpoint holds the split until every chromosome is hooked on. Taxanes and vinca alkaloids freeze the spindle so the cell is stuck at this checkpoint until it dies.

## Summary

In prometaphase, unattached kinetochores recruit MPS1, MAD1/MAD2, BUB1/BUBR1 to assemble the mitotic checkpoint complex, which inhibits APC/C-CDC20, keeping securin and cyclin B intact so anaphase cannot start. Once all kinetochores are attached under tension (Aurora B corrects mis-attachments), the checkpoint silences, separase cleaves cohesin, and chromosomes segregate; PLK1 and Aurora A drive spindle assembly and centrosome maturation, KIF18A tames chromosome oscillation. Microtubule drugs (taxanes, epothilones, eribulin stabilise or sequester; vinca alkaloids and ADC payloads MMAE/DM1 destabilise) cause persistent checkpoint activation; cells either die in mitosis (BCL-XL degradation, MCL-1 loss) or 'slip' into a tetraploid G1 where p53 arrests them, which is why TP53 loss tolerates slippage and drives aneuploidy. Whole-genome doubling and chromosomal instability arise here; CIN-high tumours depend on KIF18A, the checkpoint and BCL-XL. Aurora, PLK1 and MPS1 inhibitors have narrow windows; alisertib is being retested in SCLC and neuroendocrine prostate cancer.

## Fields

- Kind: Pathway
- Last checked: 2026-09-09
- Tags: mechanism; mechanics-atlas
- Analogy: A tug-of-war where the referee (spindle checkpoint) will not blow the whistle until every player has a grip on the rope. Taxanes glue the rope so nobody can pull; the match never starts and the players eventually collapse. Cells without p53 sneak off the pitch with the wrong number of players, which is how aneuploidy begins.
- Interventions: Taxanes (paclitaxel, docetaxel, cabazitaxel), eribulin, vinca alkaloids (vincristine, vinblastine, vinorelbine); Tubulin-payload ADCs: MMAE (enfortumab, brentuximab, polatuzumab vedotin), DM1 (T-DM1), DM4 (mirvetuximab); Aurora A (alisertib), PLK1 and MPS1 inhibitors; KIF18A inhibitors for CIN-high tumours (trials); BCL-XL degraders to tip arrested cells into death

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Spindle_checkpoint
- Musacchio & Salmon, The spindle-assembly checkpoint in space and time (Nat Rev Mol Cell Biol 2007): https://doi.org/10.1038/nrm2163

## Connected records

- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/)
- targets: [APC](https://onco.cc/targets/apc/), [BCL-2](https://onco.cc/targets/bcl2/), [BUB1](https://onco.cc/targets/bub1/), [BUB1B](https://onco.cc/targets/bub1b/), [CD30](https://onco.cc/targets/cd30/), [Folate receptor alpha](https://onco.cc/targets/folr1/), [HER2](https://onco.cc/targets/her2/), [MPS1 (TTK)](https://onco.cc/targets/ttk/), [MXI1](https://onco.cc/targets/mxi1/), [Nectin-4](https://onco.cc/targets/nectin4/), [PLK1](https://onco.cc/targets/plk1/), [RPS27](https://onco.cc/targets/rps27/), [TP53](https://onco.cc/targets/tp53/)
- drugs: [Brentuximab vedotin](https://onco.cc/drugs/brentuximab-vedotin/), [Cabazitaxel](https://onco.cc/drugs/cabazitaxel/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Enfortumab vedotin](https://onco.cc/drugs/enfortumab-vedotin/), [Eribulin](https://onco.cc/drugs/eribulin/), [Mirvetuximab soravtansine](https://onco.cc/drugs/mirvetuximab-soravtansine/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Trastuzumab emtansine](https://onco.cc/drugs/trastuzumab-emtansine/), [Vinblastine](https://onco.cc/drugs/vinblastine/), [Vincristine](https://onco.cc/drugs/vincristine/), [Vinorelbine](https://onco.cc/drugs/vinorelbine/)
- pathways: [Chromosomal instability & aneuploidy](https://onco.cc/pathways/chromosomal-instability/), [Intrinsic apoptosis (BCL-2 family)](https://onco.cc/pathways/apoptosis-bcl2/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [The cell-cycle engine (cyclins & CDKs)](https://onco.cc/pathways/cell-cycle-engine-cdks/)
- terms: [Aneuploidy and chromosomal instability as the cause of cancer](https://onco.cc/terms/aneuploidy-theory-of-cancer/), [Checkpoint (two meanings)](https://onco.cc/terms/checkpoint/), [DM1](https://onco.cc/terms/dm1/), [DM4](https://onco.cc/terms/dm4/), [MMAE](https://onco.cc/terms/mmae/), [Tubulin inhibitor payloads](https://onco.cc/terms/tubulin-inhibitor-payloads/), [Whole-genome doubling (WGD)](https://onco.cc/terms/whole-genome-doubling/)
- key papers: [Molecular characterisation of neuroendocrine prostate cancer and identification of new drug targets](https://onco.cc/key-papers/paper-beltran-nepc-aurka-mycn-cancer-discov-2011/), [The spindle-assembly checkpoint in space and time](https://onco.cc/key-papers/paper-musacchio-nat-rev-mol-cell-biol/)

---
JSON: https://onco.cc/api/v1/entities/mitotic-spindle-checkpoint.json