Shugoshin collaborates with protein phosphatase 2A to protect cohesin
Shugoshin collaborates with protein phosphatase 2A to protect cohesin
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DOI：
10.1038/nature04663
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发表时间：
2006-05-04
期刊：
影响因子：
64.8
通讯作者：
Watanabe, Y
中科院分区：
文献类型：
--
作者：
Kitajima, TS;Sakuno, T;Watanabe, Y
姐妹染色单体的凝聚力，由一种称为凝聚素的复合物介导，对于有丝分裂和减数分裂中染色体的正确分离至关重要，特别是在着丝粒处。在动物有丝分裂细胞中，磷酸化的粘附素促进其从染色体上解离，但着丝粒粘附素受到shugoshin的保护，直到着丝粒被纺锤体微管正确捕获。然而，shugoshin依赖性保护cohesin的机制尚不清楚。在这里，我们发现一个特定的亚型丝氨酸/苏氨酸蛋白磷酸酶2A（PP 2A）与人类shugoshin。PP 2A与shugoshin共定位于着丝粒，并且是着丝粒保护所必需的。纯化的shugoshin复合物在体外具有逆转cohesin磷酸化的能力，表明cohesin的去磷酸化是保护着丝粒的机制。裂殖酵母的减数分裂shugoshin也与PP 2A相关联，这两种蛋白质协同保护着丝粒处含有Rec 8的粘着蛋白。因此，我们揭示了真核细胞染色体在有丝分裂和减数分裂中的着丝粒保护的保守机制。
Sister chromatid cohesion, mediated by a complex called cohesin, is crucial-particularly at centromeres-for proper chromosome segregation in mitosis and meiosis. In animal mitotic cells, phosphorylation of cohesin promotes its dissociation from chromosomes, but centromeric cohesin is protected by shugoshin until kinetochores are properly captured by the spindle microtubules. However, the mechanism of shugoshin-dependent protection of cohesin is unknown. Here we find a specific subtype of serine/threonine protein phosphatase 2A (PP2A) associating with human shugoshin. PP2A colocalizes with shugoshin at centromeres and is required for centromeric protection. Purified shugoshin complex has an ability to reverse the phosphorylation of cohesin in vitro, suggesting that dephosphorylation of cohesin is the mechanism of protection at centromeres. Meiotic shugoshin of fission yeast also associates with PP2A, with both proteins collaboratively protecting Rec8-containing cohesin at centromeres. Thus, we have revealed a conserved mechanism of centromeric protection of eukaryotic chromosomes in mitosis and meiosis.