Phosphorylation of H2A by Bub1 Prevents Chromosomal Instability Through Localizing Shugoshin
Phosphorylation of H2A by Bub1 Prevents Chromosomal Instability Through Localizing Shugoshin
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DOI：
10.1126/science.1180189
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发表时间：
2010-01-08
期刊：
影响因子：
56.9
通讯作者：
Watanabe, Yoshinori
中科院分区：
文献类型：
--
作者：
Kawashima, Shigehiro A.;Yamagishi, Yuya;Watanabe, Yoshinori
Bub 1是一种多功能蛋白激酶，在真核生物中，它是染色体分离所必需的。人类Bub 1的损伤可能导致染色体不稳定性（CIN）或肿瘤发生。然而，Bub 1的主要细胞底物仍然难以捉摸。在这里，我们表明，Bub 1磷酸化组蛋白H2 A的保守丝氨酸121裂殖酵母粟酒裂殖酵母。其中所有细胞H2 A-S121被丙氨酸取代的h2 a-SA突变体在失去shugoshin蛋白质的着丝粒定位方面表型模仿bub 1激酶死亡突变体（bub 1-KD）。将shugoshin人工拴系到着丝粒在很大程度上恢复了h2 a-SA或bub 1-KD相关的CIN缺陷，这是一种进化上保守的功能。因此，Bub 1激酶为shugoshin定位和染色体的正确分配创造了一个标记。
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.