Tousled-like kinase functions with the chromatin assembly pathway regulating nuclear divisions
Tousled-like kinase functions with the chromatin assembly pathway regulating nuclear divisions
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DOI：
10.1101/gad.276703
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发表时间：
2003-10-15
影响因子：
10.5
通讯作者：
Karch, F
中科院分区：
文献类型：
--
作者：
Carrera, P;Moshkin, YM;Karch, F
Tousled样激酶（TLKs）是一类在植物和动物中保守的丝氨酸/苏氨酸激酶家族，其作用依赖于细胞周期。在哺乳动物中，它们的活性在S期达到峰值，此时它们磷酸化抗沉默功能蛋白1（ASF 1），这是一种参与复制依赖性染色质组装的组蛋白伴侣。在这里，我们表明，果蝇ASF 1也是TLK的磷酸化目标，这两个组件合作，以控制染色质在体内复制。通过功能丧失突变改变TLK活性，我们发现核分裂在间期被阻止，然后是凋亡。TLK的过表达改变染色质结构，表明TLK介导染色质蛋白的活性。这些结果表明，TLK通过调节染色质动力学来协调细胞周期进程。
Tousled-like kinases (TLKs) constitute a family of serine/threonine kinases conserved in plants and animals that act in a cell cycle-dependent manner. In mammals, their activity peaks during S phase, when they phosphorylate the antisilencing function protein 1 (ASF1), a histone chaperone involved in replication-dependent chromatin assembly. Here, we show that Drosophila ASF1 is also a phosphorylation target of TLK, and that the two components cooperate to control chromatin replication in vivo. By altering TLK activity through loss-of-function mutations, we show that nuclear divisions are arrested at interphase, followed by apoptosis. Overexpression of TLK alters the chromatin structure, suggesting that TLK mediates the activity of chromatin proteins. These results suggest that TLK coordinates cell cycle progression through the regulation of chromatin dynamics.