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Published online
doi:10.1083/jcb.200701122
The Journal of Cell Biology, Vol. 177, No. 3, 413-424
The Rockefeller University Press, 0021-9525 $30.00
© Huang et al.
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Article

Tripin/hSgo2 recruits MCAK to the inner centromere to correct defective kinetochore attachments



Haomin Huang1,4, Jie Feng1, Jakub Famulski2, Jerome B. Rattner3, Song Tao Liu1, Gary D. Kao4, Ruth Muschel5, Gordon K.T. Chan2, and Tim J. Yen1

1 Fox Chase Cancer Center, Philadelphia, PA 19111
2 Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 1Z2, Canada
3 Department of Cell Biology and Anatomy, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada
4 Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104
5 Radiation Oncology and Biology, Oxford University, Oxford OX3 7LJ, England, UK

Correspondence to T.J. Yen: tj_yen{at}fccc.edu

hSgo2 (previously annotated as Tripin) was recently reported to be a new inner centromere protein that is essential for centromere cohesion (Kitajima et al., 2006). In this study, we show that hSgo2 exhibits a dynamic distribution pattern, and that its localization depends on the BUB1 and Aurora B kinases. hSgo2 is concentrated at the inner centromere of unattached kinetochores, but extends toward the kinetochores that are under tension. This localization pattern is reminiscent of MCAK, which is a microtubule depolymerase that is believed to be a key component of the error correction mechanism at kinetochores. Indeed, we found that hSgo2 is essential for MCAK to localize to the centromere. Delocalization of MCAK accounts for why cells depleted of hSgo2 exhibit kinetochore attachment defects that go uncorrected, despite a transient delay in the onset of anaphase. Consequently, these cells exhibit a high frequency of lagging chromosomes when they enter anaphase. We confirmed that hSgo2 is associated with PP2A, and we propose that it contributes to the spatial regulation of MCAK activity within inner centromere and kinetochore.

Abbreviation used in this paper: ACA, anticentromere antibodies.


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