Probing Spindle Assembly Mechanisms with Monastrol, a Small Molecule Inhibitor of the Mitotic Kinesin, Eg5
By T. Kapoor, T. Mayer, M. Coughlin, T. Mitchison. Journal of Cell Biology, 2000
752 citations recorded by the source corpus.
Monastrol, a cell-permeable small molecule inhibitor of the mitotic kinesin, Eg5, arrests cells in mitosis with monoastral spindles. Here, we use monastrol to probe mitotic mechanisms. We find that monastrol does not inhibit progression through S and G2 phases of the cell cycle or centrosome duplication. The mitotic arrest due to monastrol is also rapidly reversible. Chromosomes in monastrol-treated cells frequently have both sister kinetochores attached to microtubules extending to the center of the monoaster (syntelic orientation). Mitotic arrest–deficient protein 2 (Mad2) localizes to a subset of kinetochores, suggesting the activation of the spindle assembly checkpoint in these cells. Mad2 localizes to some kinetochores that have attached microtubules in monastrol-treated cells, indicating that kinetochore microtubule attachment alone may not satisfy the spindle assembly checkpoint. Monastrol also inhibits bipolar spindle formation in Xenopus egg extracts. However, it does not prevent the targeting of Eg5 to the monoastral spindles that form. Imaging bipolar spindles disassembling in the presence of monastrol allowed direct observations of outward directed forces in the spindle, orthogonal to the pole-to-pole axis. Monastrol is thus a useful tool to study mitotic processes, detection and correction of chromosome malorientation, and contributions of Eg5 to spindle assembly and maintenance.
Subfields: Cell Biology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/48f5f9819e3dfafc54035b7b2eba0085acaa675c
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Citations in the corpus
- The spindle checkpoint: structural insights into dynamic signalling (2002, background): “Syntelic chromosomes (chromosomes with both sisters attached to the same pole) often retain Mad2 at their kinetochore”
- The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore–microtubule attachment and in maintaining the spindle assembly checkpoint (2003, background): “Under this condition, cells arrest in mitosis for at least 5 h with 70% of their chromosomes syntelically monooriented, whereas the remainder are monotelically monooriented (Kapoor et al., 2000).”
- Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial (2017, background): “Progression-free 6-mo survival rate 56 (51-61) 37 (30-44) 19 (15-23)”
- Kinetochore microtubule dynamics and attachment stability are regulated by Hec1. (2006, neutral): “PtK1 cells with monopolar spindles (generated by addition of 200 mM monastrol; Mayer et al.,1999; Kapoor et al., 2000), were injected with buffer alone or 9G3 and imaged by timelapse phase-contrast microscopy.”