Dynamic Phosphorylation of CENP-A at Ser68 Orchestrates Its Cell-Cycle-Dependent Deposition at Centromeres
Dynamic Phosphorylation of CENP-A at Ser68 Orchestrates Its Cell-Cycle-Dependent Deposition at Centromeres
复制标题
CENP-A Ser68 处的动态磷酸化协调其在着丝粒上的细胞周期依赖性沉积
DOI：
10.1016/j.devcel.2014.11.030
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发表时间：
2015-01-12
影响因子：
11.8
通讯作者：
Li, Guohong
中科院分区：
文献类型：
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作者：
Yu, Zhouliang;Zhou, Xiang;Li, Guohong
H3组蛋白变体CENP-A是对着丝粒身份和功能至关重要的表观遗传标记。然而，在细胞周期中，CENP-A在着丝粒的时空沉积和繁殖的精确调控仍然知之甚少。在这里，我们发现CENP-A在有丝分裂早期被Cdk1磷酸化至Ser68位点。我们的研究结果表明，Ser68的磷酸化消除了CENP-A与组装因子HJURP的结合，从而防止了CENP-A在有丝分裂退出之前过早装载到着丝粒上。由于Cdk1活性在有丝分裂出口处于最低水平，Cdk1/PP1 α活性的比值变化有利于Ser68去磷酸化，从而使CENP-A可用于HJURP的着丝粒沉积。因此，我们揭示了在细胞周期中，CENP-A Ser68的动态磷酸化协调了新合成的CENP-A在活性着丝粒上的时空组装。
The H3 histone variant CENP-A is an epigenetic marker critical for the centromere identity and function. However, the precise regulation of the spatiotemporal deposition and propagation of CENP-A at centromeres during the cell cycle is still poorly understood. Here, we show that CENP-A is phosphorylated at Ser68 during early mitosis by Cdk1. Our results demonstrate that phosphorylation of Ser68 eliminates the binding of CENP-A to the assembly factor HJURP, thus preventing the premature loading of CENP-A to the centromere prior to mitotic exit. Because Cdk1 activity is at its minimum at the mitotic exit, the ratio of Cdk1/PP1 alpha activity changes in favor of Ser68 dephosphorylation, thus making CENP-A available for centromeric deposition by HJURP. Thus, we reveal that dynamic phosphorylation of CENP-A Ser68 orchestrates the spatiotemporal assembly of newly synthesized CENP-A at active centromeres during the cell cycle.