Reference - Detail
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 | 41.846 |
Times Cited | 283 |
WOS Category | CELL BIOLOGY |
Resource | |
Yeast | FY13784(PZ865) FY13775(PZ405) FY13792(PZ946) FY13818(PX536) FY13787(PZ901) FY13784(PZ865) FY13504(JX794) ? |