Bub1 对 H2A 的磷酸化作用通过定位 shugoshin 来防止染色体不稳定性。

Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin.

机构信息

Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.

出版信息

Science. 2010 Jan 8;327(5962):172-7. doi: 10.1126/science.1180189. Epub 2009 Nov 19.

DOI:10.1126/science.1180189

PMID:19965387

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.

摘要

Bub1 是一种在真核生物中用于正确染色体分离的多功能蛋白激酶。Bub1 在人类中的功能障碍可能导致染色体不稳定（CIN）或肿瘤发生。然而，Bub1 的主要细胞底物仍然难以捉摸。在这里，我们表明 Bub1 在裂殖酵母 Schizosaccharomyces pombe 中磷酸化组蛋白 H2A 的保守丝氨酸 121。h2a-SA 突变体，其中所有细胞 H2A-S121 都被丙氨酸取代，表现出失去着丝粒蛋白的 Bub1 激酶失活突变体（bub1-KD）的表型。人工将 shugoshin 束缚到着丝粒上，在很大程度上恢复了 h2a-SA 或 bub1-KD 相关的 CIN 缺陷，这一功能在进化上是保守的。因此，Bub1 激酶为 shugoshin 的定位和染色体的正确分配创建了一个标记。