Bub1 is a protein kinase required for proper chromosome segregation, which was found eighteen years ago. While Bub1 is required for suppressing tumorigenesis, the canonical cellular substrate of Bub1 still remains to be identified. Here we identified histone H2A as the primary substrate of Bub1. This phosphorylation ultimately localizes shugoshin and thereby ensuring proper partition of chromosomes. We further demonstrate that the Bub1 pathway identified in fission yeast is highly conserved in human cells. Shugoshin is also required for proper meiosis. Therefore, our findings are useful for revealing the fundamental mechanisms of tumorigenesis or Down syndrom, which are related to chromosomal instability in humans.

Program member
Yoshinori Watanabe (Institute of Molecular and Cellular Biosciences)