Shugoshin-PP2A counteracts casein-kinase-1-dependent cleavage of Rec8 by separase
Shugoshin-PP2A counteracts casein-kinase-1-dependent cleavage of Rec8 by separase
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DOI：
10.1038/ncb2052
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发表时间：
2010-05-01
影响因子：
21.3
通讯作者：
Watanabe, Yoshinori
中科院分区：
文献类型：
--
作者：
Ishiguro, Tadashi;Tanaka, Koichi;Watanabe, Yoshinori
在减数分裂过程中，维持姐妹染色单体凝聚力的凝聚素复合物以逐步的方式丢失（1，2）。在减数分裂Ⅰ，粘连蛋白亚基Rec 8仅沿着染色体臂裂解;在减数分裂Ⅱ之前，它在着丝粒处受到shugoshin（Sgo 1）-蛋白磷酸酶2A（PP 2A）的保护（3-5）。虽然这种调节假设涉及被Sgo 1-PP 2A拮抗的磷酸化，但负责的激酶和底物尚不清楚（6，7）。使用“抗-shugoshin”的遗传筛选，我们鉴定了Hhp 2，酪蛋白激酶1 delta/β（CK 1）的直向同源物，作为裂殖酵母中Rec 8裂解所需的因子。我们表明，CK 1，而不是一个Polo样激酶，被广泛认为是这样做，作为凝聚蛋白激酶，以促进这种分裂过程中减数分裂。重要的是，在近着丝粒区域强制定位过量Hhp 2废除了Sgo 1-PP 2A保护着丝粒Rec 8的能力。因此，我们的研究证明了一个关键的概念，即Rec 8磷酸化和Sgo 1-PP 2A去磷酸化之间的平衡调节减数分裂中染色体凝聚力的逐步丧失。
During meiosis, the cohesin complexes that maintain sister chromatid cohesion are lost in a stepwise manner(1,2). At meiosis I the cohesin subunit Rec8 is cleaved only along the chromosome arms; until meiosis II it is protected at centromeres by the action of shugoshin (Sgo1)-protein phosphatase 2A (PP2A)(3-5). Although this regulation hypothetically involves phosphorylation that is antagonized by Sgo1-PP2A, the kinase and substrate that are responsible are as yet unknown(6,7). Using a genetic screen for 'anti-shugoshin', we identify Hhp2, an orthologue of casein kinase 1 delta/epsilon (CK1), as a factor required for Rec8 cleavage in fission yeast. We show that CK1, rather than a Polo-like kinase that is widely believed to do so, acts as the cohesin kinase to promote this cleavage during meiosis. Crucially, forced localization of excess Hhp2 at the pericentromeric region abrogates the ability of Sgo1-PP2A to protect centromeric Rec8. Thus, our studies prove the key notion that the balance between Rec8 phosphorylation and its dephosphorylation by Sgo1-PP2A regulates the step-wise loss of chromosomal cohesion in meiosis.