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Tension sensing by Aurora B kinase is independent of survivin-based centromere localization

Nature volume 497, pages 118–121 (2013)Cite this article

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Abstract

Accurate segregation of the replicated genome requires chromosome biorientation on the spindle. Biorientation is ensured by Aurora B kinase (Ipl1), a member of the four-subunit chromosomal passenger complex (CPC)1,2. Localization of the CPC to the inner centromere is central to the current model for how tension ensures chromosome biorientation: kinetochore–spindle attachments that are not under tension remain close to the inner centromere and are destabilized by Aurora B phosphorylation, whereas kinetochores under tension are pulled away from the influence of Aurora B, stabilizing their microtubule attachments3,4,5. Here we show that an engineered truncation of the Sli15 (known as INCENP in humans) subunit of budding yeast CPC that eliminates association with the inner centromere nevertheless supports proper chromosome segregation during both mitosis and meiosis. Truncated Sli15 suppresses the deletion phenotypes of the inner-centromere-targeting proteins survivin (Bir1), borealin (Nbl1), Bub1 and Sgo1 (ref. 6). Unlike wild-type Sli15, truncated Sli15 localizes to pre-anaphase spindle microtubules. Premature targeting of full-length Sli15 to microtubules by preventing Cdk1 (also known as Cdc28) phosphorylation also suppresses the inviability of Bir1 deletion. These results suggest that activation of Aurora B kinase by clustering either on chromatin or on microtubules is sufficient for chromosome biorientation.

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Figure 1: Deletion of the Sli15 N terminus prevents association with Bir1 but does not affect cell viability or growth.
Figure 2: sli15(ΔNT) suppresses lethality of bir1Δ and nbl1Δ, and shows normal fidelity mitotic and meiotic chromosome segregation.
Figure 3: sli15(ΔNT) suppresses mutants in the Bir1-dependent CPC-targeting pathway but is synthetically lethal with genes implicated in centromere cohesion.
Figure 4: Localization of Sli15(ΔNT) and relationship between Sli15 microtubule localization and suppression of bir1Δ.

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Acknowledgements

The authors would like to thank the Desai and Oegema laboratories for discussions; S. Sandall, H. Hu and E. Manrriquez for assistance; B. Ren’s laboratory for help with ChIP experiments; S. Biggins, D. Dawson, G. Pereira, G. Barnes, P. Hieter and the Yeast Resource Center for strains and plasmids; and K. Oegema, R. Green and J. DeLuca for comments on the manuscript. This work was supported by a National Institutes of Health (NIH) grant (GM074215) to A.D. and a Damon Runyon Cancer Research Foundation Fellowship (DRG 2007-09) to C.S.C. A.D. receives salary and other support from the Ludwig Institute for Cancer Research.

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  1. Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, 92037, California, USA

    Christopher S. Campbell & Arshad Desai

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  1. Christopher S. Campbell
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C.S.C. and A.D. designed experiments and wrote the manuscript. C.S.C. performed the experiments and analysed the data.

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Correspondence to Arshad Desai.

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Campbell, C., Desai, A. Tension sensing by Aurora B kinase is independent of survivin-based centromere localization. Nature 497, 118–121 (2013). https://doi.org/10.1038/nature12057

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