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¹ Research Institute of Molecular Pathology, 1030 Vienna, Austria
² Laboratory for Cell Regulation, Wadsworth Center for Laboratories and Research, Albany, NY 12201
³ Boehringer Ingelheim Pharma KG, 88397 Biberach/Riss, Germany
⁴ Boehringer Ingelheim Austria, 1121 Vienna, Austria

Address correspondence to Jan-Michael Peters, Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria. Tel.: 43-1-797-30-886. Fax: 43-1-798-71-53. E-mail: peters{at}imp.univie.ac.at

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.

Key Words: mitosis; chromosome segregation; kinetochores; spindle assembly checkpoint; chemical biology

^* Abbreviations used in this paper: APC, anaphase-promoting complex; NEB, nuclear envelope breakdown; RNAi, RNA interference; siRNA, small inhibitory RNA.

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• Ohi, R., Sapra, T., Howard, J., Mitchison, T. J. (2004). Differentiation of Cytoplasmic and Meiotic Spindle Assembly MCAK Functions by Aurora B-dependent Phosphorylation. Mol. Biol. Cell 15: 2895-2906 [Abstract] [Full Text]  
• Logarinho, E., Bousbaa, H., Dias, J. M., Lopes, C., Amorim, I., Antunes-Martins, A., Sunkel, C. E. (2004). Different spindle checkpoint proteins monitor microtubule attachment and tension at kinetochores in Drosophila cells. J. Cell Sci. 117: 1757-1771 [Abstract] [Full Text]  
• Johnson, V. L., Scott, M. I. F., Holt, S. V., Hussein, D., Taylor, S. S. (2004). Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression. J. Cell Sci. 117: 1577-1589 [Abstract] [Full Text]  
• Kline-Smith, S. L., Khodjakov, A., Hergert, P., Walczak, C. E. (2004). Depletion of Centromeric MCAK Leads to Chromosome Congression and Segregation Defects Due to Improper Kinetochore Attachments. Mol. Biol. Cell 15: 1146-1159 [Abstract] [Full Text]  
• Glotzer, M. (2004). Cleavage furrow positioning. J. Cell Biol. 164: 347-351 [Abstract] [Full Text]  
• Sun, F., Betzendahl, I., Shen, Y., Cortvrindt, R., Smitz, J., Eichenlaub-Ritter, U. (2004). Preantral follicle culture as a novel in vitro assay in reproductive toxicology testing in mammalian oocytes. Mutagenesis 19: 13-25 [Abstract] [Full Text]  
• Prigent, C., Dimitrov, S. (2003). Phosphorylation of serine 10 in histone H3, what for?. J. Cell Sci. 116: 3677-3685 [Abstract] [Full Text]  

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