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The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore–microtubule attachment and in maintaining the spindle assembly checkpoint
Open accessAbstract
The proper segregation of sister chromatids in mitosis depends on bipolar attachment of all chromosomes to the mitotic spindle. We have identified the small molecule Hesperadin as an inhibitor of chromosome alignment and segregation. Our data imply that Hesperadin causes this phenotype by inhibiting the function of the mitotic kinase Aurora B. Mammalian cells treated with Hesperadin enter anaphase in the presence of numerous monooriented chromosomes, many of which may have both sister kinetochores attached to one spindle pole (syntelic attachment). Hesperadin also causes cells arrested by taxol or monastrol to enter anaphase within <1 h, whereas cells in nocodazole stay arrested for 3–5 h. Together, our data suggest that Aurora B is required to generate unattached kinetochores on monooriented chromosomes, which in turn could promote bipolar attachment as well as maintain checkpoint signaling.
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Cites
Dynamic instability of microtubule growth
Mitchison, T., & Kirschner, M. (1984) · Nature · doi:10.1038/312237a0 · Cited by 3,337
Nasmyth, K. (2001) · Annual Review of Genetics · doi:10.1146/annurev.genet.35.102401.091334 · Cited by 805
Cited by
The spindle-assembly checkpoint in space and time
Musacchio, A., & Salmon, E. D. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2163 · Cited by 2,227
Tetraploidy, aneuploidy and cancer
Ganem, N. J., Storchova, Z., & Pellman, D. (2007) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2007.02.011 · Cited by 668
Wang, I.-C., Chen, Y.-J., Hughes, D., Petrovic, V., Major, M. L., Park, H. J., Tan, Y., Ackerson, T., & Costa, R. H. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.10875-10894.2005 · Cited by 627
Shared and separate functions of polo-like kinases and aurora kinases in cancer
Lens, S. M. A., Voest, E. E., & Medema, R. H. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2964 · Cited by 597
Examining the link between chromosomal instability and aneuploidy in human cells
Thompson, S. L., & Compton, D. A. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200712029 · Cited by 521
Metadata
- Authors
- Hauf, S., Cole, R. W., LaTerra, S., Zimmer, C., Schnapp, G., Walter, R., Heckel, A., van Meel, J., Rieder, C. L., & Peters, J.-M.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2003-04-21
- Volume
- 161
- Issue
- 2
- Pages
- 281-294
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2106942695
- Cited by
- 1,155
- References
- 2
- FWCI
- 21.55
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore–microtubule attachment and in maintaining the spindle assembly checkpoint. https://app.cochat.ai/papers/10.1083/jcb.200208092
- The paper
- Hauf, S., Cole, R. W., LaTerra, S., Zimmer, C., Schnapp, G., Walter, R., Heckel, A., van Meel, J., Rieder, C. L., & Peters, J.-M. (2003). The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore–microtubule attachment and in maintaining the spindle assembly checkpoint. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200208092
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