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Science 327 (5962): 172-177

Copyright © 2010 by the American Association for the Advancement of Science

Phosphorylation of H2A by Bub1 Prevents Chromosomal Instability Through Localizing Shugoshin

Shigehiro A. Kawashima,1 Yuya Yamagishi,1,2,* Takashi Honda,1,3,* Kei-ichiro Ishiguro,1 Yoshinori Watanabe1,2,3,{dagger}

Abstract: Bub1 is a multi-task protein kinase required for proper chromosome segregation in eukaryotes. Impairment of Bub1 in humans may lead to chromosomal instability (CIN) or tumorigenesis. Yet, the primary cellular substrate of Bub1 has remained elusive. Here, we show that Bub1 phosphorylates the conserved serine 121 of histone H2A in fission yeast Schizosaccharomyces pombe. The h2a-SA mutant, in which all cellular H2A-S121 is replaced by alanine, phenocopies the bub1 kinase-dead mutant (bub1-KD) in losing the centromeric localization of shugoshin proteins. Artificial tethering of shugoshin to centromeres largely restores the h2a-SA or bub1-KD–related CIN defects, a function that is evolutionally conserved. Thus, Bub1 kinase creates a mark for shugoshin localization and the correct partitioning of chromosomes.

1 Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
2 Graduate Program in Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
3 Graduate School of Agricultural and Life Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ywatanab{at}iam.u-tokyo.ac.jp

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