Phosphorylation of H2A by Bub1 Prevents Chromosomal Instability Through Localizing Shugoshin

被引：379

作者：

Kawashima, Shigehiro A. ^{[1
]}

Yamagishi, Yuya ^{[1
,2
]}

Honda, Takashi ^{[1
,3
]}

Ishiguro, Kei-ichiro ^{[1
]}

Watanabe, Yoshinori ^{[1
,2
,3
]}

机构：

[1] Univ Tokyo, Inst Mol & Cellular Biosci, Lab Chromosome Dynam, Tokyo 1130032, Japan

[2] Univ Tokyo, Grad Sch Sci, Grad Program Biophys & Biochem, Tokyo 1130032, Japan

[3] Univ Tokyo, Grad Sch Agr & Life Sci, Tokyo 1130032, Japan

来源：

SCIENCE | 2010年 / 327卷 / 5962期

基金：

日本学术振兴会;

关键词：

SISTER-CHROMATID COHESION; PROTEIN PHOSPHATASE 2A; FISSION YEAST BUB1; SPINDLE CHECKPOINT; MEIOSIS-I; CENTROMERIC PROTECTION; KINASE-ACTIVITY; KINETOCHORE; MITOSIS; LOCALIZATION;

D O I：

10.1126/science.1180189

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：172 / 177

页数：6

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