RRC ID 12469
Author Kawashima SA, Yamagishi Y, Honda T, Ishiguro K, Watanabe Y.
Title Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin.
Journal Science
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.
Volume 327(5962)
Pages 172-7
Published 2010-1-8
DOI 10.1126/science.1180189
PII science.1180189
PMID 19965387
MeSH Animals Centromere / metabolism* Chromosomal Instability* Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism* Chromosome Segregation* Chromosomes, Fungal / metabolism Histones / metabolism* Humans Kinetochores / metabolism Meiosis Mice Mitosis Nucleosomes / metabolism Phosphorylation Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism* Recombinant Proteins / metabolism Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae / metabolism Saccharomyces cerevisiae Proteins / genetics Saccharomyces cerevisiae Proteins / metabolism Schizosaccharomyces / cytology Schizosaccharomyces / genetics Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Serine / metabolism
IF 41.058
Times Cited 194
Yeast FY13784(PZ865) FY13775(PZ405) FY13792(PZ946) FY13818(PX536) FY13787(PZ901) FY13784(PZ865) FY13504(JX794) ?