Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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.

References

  1. 1

    Ruchaud, S., Carmena, M. & Earnshaw, W. C. Chromosomal passengers: conducting cell division. Nature Rev. Mol. Cell Biol. 8, 798–812 (2007)

    CAS  Article  Google Scholar 

  2. 2

    Pinsky, B. A. & Biggins, S. The spindle checkpoint: tension versus attachment. Trends Cell Biol. 15, 486–493 (2005)

    CAS  Article  PubMed  Google Scholar 

  3. 3

    Tanaka, T. U. et al. Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. Cell 108, 317–329 (2002)

    CAS  Article  PubMed  Google Scholar 

  4. 4

    Liu, D., Vader, G., Vromans, M. J. M., Lampson, M. A. & Lens, S. M. A. Sensing chromosome bi-orientation by spatial separation of Aurora B kinase from kinetochore substrates. Science 323, 1350–1353 (2009)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5

    Lampson, M. A. & Cheeseman, I. M. Sensing centromere tension: Aurora B and the regulation of kinetochore function. Trends Cell Biol. 21, 133–140 (2011)

    CAS  Article  PubMed  Google Scholar 

  6. 6

    Kawashima, S. A., Yamagishi, Y., Honda, T., Ishiguro, K.-I. & Watanabe, Y. Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin. Science 327, 172–177 (2010)

    ADS  CAS  Article  PubMed  Google Scholar 

  7. 7

    Yoon, H. J. & Carbon, J. Participation of Bir1p, a member of the inhibitor of apoptosis family, in yeast chromosome segregation events. Proc. Natl Acad. Sci. USA 96, 13208–13213 (1999)

    ADS  CAS  Article  PubMed  Google Scholar 

  8. 8

    Cho, U.-S. & Harrison, S. C. Ndc10 is a platform for inner kinetochore assembly in budding yeast. Nature Struct. Mol. Biol. 19, 48–55 (2012)

    CAS  Article  Google Scholar 

  9. 9

    Yamagishi, Y., Honda, T., Tanno, Y. & Watanabe, Y. Two histone marks establish the inner centromere and chromosome bi-orientation. Science 330, 239–243 (2010)

    ADS  CAS  Article  PubMed  Google Scholar 

  10. 10

    Kelly, A. E. et al. Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B. Science 330, 235–239 (2010)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11

    Wang, F. et al. Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis. Science 330, 231–235 (2010)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12

    Shimogawa, M. M., Widlund, P. O., Riffle, M., Ess, M. & Davis, T. N. Bir1 is required for the tension checkpoint. Mol. Biol. Cell 20, 915–923 (2009)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13

    Makrantoni, V. & Stark, M. Efficient chromosome bi-orientation and the tension checkpoint in Saccharomyces cerevisiae both require Bir1. Mol. Cell. Biol. 29, 4552–4562 (2009)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14

    Sandall, S. et al. A Bir1-Sli15 complex connects centromeres to microtubules and is required to sense kinetochore tension. Cell 127, 1179–1191 (2006)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15

    Jeyaprakash, A. A. et al. Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. Cell 131, 271–285 (2007)

    CAS  Article  PubMed  Google Scholar 

  16. 16

    Biggins, S. & Murray, A. W. The budding yeast protein kinase Ipl1/Aurora allows the absence of tension to activate the spindle checkpoint. Genes Dev. 15, 3118–3129 (2001)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17

    Kim, J. H., Kang, J. S. & Chan, C. S. Sli15 associates with the ipl1 protein kinase to promote proper chromosome segregation in Saccharomyces cerevisiae. J. Cell Biol. 145, 1381–1394 (1999)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. 18

    Indjeian, V. B. The centromeric protein Sgo1 is required to sense lack of tension on mitotic chromosomes. Science 307, 130–133 (2005)

    ADS  CAS  Article  PubMed  Google Scholar 

  19. 19

    Li, R. & Murray, A. W. Feedback control of mitosis in budding yeast. Cell 66, 519–531 (1991)

    CAS  Article  PubMed  Google Scholar 

  20. 20

    Ng, T. M., Waples, W. G., Lavoie, B. D. & Biggins, S. Pericentromeric sister chromatid cohesion promotes kinetochore biorientation. Mol. Biol. Cell 20, 3818–3827 (2009)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21

    Shonn, M. A., McCarroll, R. & Murray, A. W. Requirement of the spindle checkpoint for proper chromosome segregation in budding yeast meiosis. Science 289, 300–303 (2000)

    ADS  CAS  Article  PubMed  Google Scholar 

  22. 22

    Pereira, G. Separase regulates INCENP-Aurora B anaphase spindle function through Cdc14. Science 302, 2120–2124 (2003)

    ADS  CAS  Article  PubMed  Google Scholar 

  23. 23

    Rozelle, D. K., Hansen, S. D. & Kaplan, K. B. Chromosome passenger complexes control anaphase duration and spindle elongation via a kinesin-5 brake. J. Cell Biol. 193, 285–294 (2011)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24

    Nakajima, Y. et al. Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP regulates CPC–spindle interaction to ensure proper microtubule dynamics. J. Cell Biol. 194, 137–153 (2011)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25

    Sessa, F. et al. Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Mol. Cell 18, 379–391 (2005)

    CAS  Article  PubMed  Google Scholar 

  26. 26

    Kelly, A. E. et al. Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly. Dev. Cell 12, 31–43 (2007)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27

    Tseng, B. S., Tan, L., Kapoor, T. M. & Funabiki, H. Dual detection of chromosomes and microtubules by the chromosomal passenger complex drives spindle assembly. Dev. Cell 18, 903–912 (2010)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. 28

    Wan, X. et al. Protein architecture of the human kinetochore microtubule attachment site. Cell 137, 672–684 (2009)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29

    Longtine, M. S. et al. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 14, 953–961 (1998)

    CAS  Article  PubMed  Google Scholar 

  30. 30

    Hieter, P., Mann, C., Snyder, M. & Davis, R. W. Mitotic stability of yeast chromosomes: a colony color assay that measures nondisjunction and chromosome loss. Cell 40, 381–392 (1985)

    CAS  Article  PubMed  Google Scholar 

Download references

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.

Author information

Affiliations

Authors

Contributions

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

Corresponding author

Correspondence to Arshad Desai.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-3, Supplementary Table 1, a Supplementary Discussion and Supplementary References. (PDF 1457 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing