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Publication : Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin.

First Author  Kawashima SA Year  2010
Journal  Science Volume  327
Issue  5962 Pages  172-7
PubMed ID  19965387 Mgi Jnum  J:155745
Mgi Id  MGI:4415638 Doi  10.1126/science.1180189
Citation  Kawashima SA, et al. (2010) Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin. Science 327(5962):172-7
abstractText  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.
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