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Human Zw10 and ROD are mitotic checkpoint proteins that bind to kinetochores

Abstract

Here we show that human Zeste White 10 (Zw10) and Rough deal (Rod) are new components of the mitotic checkpoint, as cells lacking these proteins at kinetochores fail to arrest in mitosis when exposed to microtubule inhibitors. Checkpoint failure and premature mitotic exit may explain why cells defective for hZw10 and hRod divide with lagging chromosomes. As Zw10 and Rod are not conserved in yeast, our data, combined with an accompanying study of Drosophila Zw10 and Rod, indicate that metazoans may require an elaborate spindle checkpoint to monitor complex kinetochore functions.

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Figure 1: hRod and hZw10 form a complex in vivo.
Figure 2: Localization of hRod during mitosis.
Figure 3: hROD and hzw10 are essential components of the mitotic checkpoint.
Figure 4: hRod and hZw10 are not required for other checkpoint proteins to bind to kinetochores.

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Acknowledgements

We thank J. C. Hittle and H. L. Simpkins for micro-injections and for purifying hZw10 antibodies, respectively. We also thank all members of the Yen laboratory for comments and suggestions during the course of the work. This work was supported by grants to T.J.Y. from the NIH, ACS, and Leukemia and Lymphoma Society, core grant CA06927 and an appropriation from the Commonwealth of Pennsylvania. M.L.G. was supported by a grant from the NIH.

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Correspondence to T. J. Yen.

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Figure S1

Characterization of kinetochores depleted in hRod and hZW10. (PDF 628 kb)

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Chan, G., Jablonski, S., Starr, D. et al. Human Zw10 and ROD are mitotic checkpoint proteins that bind to kinetochores . Nat Cell Biol 2, 944–947 (2000). https://doi.org/10.1038/35046598

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