Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin.
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.
Kawashima
Shigehiro A
SA
Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
Yamagishi
Yuya
Y
Honda
Takashi
T
Ishiguro
Kei-ichiro
K
Watanabe
Yoshinori
Y
D000818:Animals; D002503:Centromere / Q000378:metabolism*; D043171:Chromosomal Instability; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008540:Meiosis; D051379:Mice; D008938:Mitosis; D009707:Nucleosomes / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D009707:Nucleosomes; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C485973:Sgo1 protein, S pombe; C485974:Sgo2 protein, S pombe; D012694:Serine; C495594:Bub1 protein, S pombe; D017346:Protein Serine-Threonine Kinases