Identification of human Asf1 chromatin assembly factors as substrates of Tousled-like kinases
Identification of human Asf1 chromatin assembly factors as substrates of Tousled-like kinases
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DOI：
10.1016/s0960-9822(01)00298-6
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发表时间：
2001-07-10
期刊：
影响因子：
9.2
通讯作者：
Nigg, EA
中科院分区：
文献类型：
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作者：
Silljé, HHW;Nigg, EA
Tousled-like kinases（Tlks）在植物和动物中高度保守，最早在拟南芥中被描述[1]。在植物中，Tousled激酶对于花和叶的正常发育是必不可少的，但是还没有建立与任何其它植物基因产物的直接功能联系[1，2]。同样，Tlks在动物中的作用也是未知的。在人类细胞中，两种结构相似的Tlk（Tlk 1和Tlk 2）最近被证明是细胞周期调节激酶，在S期具有最大活性[3]。在这里，我们报告了果蝇染色质组装因子Asf 1（抗沉默功能1）[4]的两个人类同源物作为Tlks的生理底物的鉴定。我们发现，人Asf 1蛋白磷酸化Tlks在体内和体外。此外，Asf 1蛋白在S期被磷酸化，此时Tlks最活跃。相反，Asf 1蛋白在DNA复制检查点激活后去磷酸化，伴随着Tlks的快速失活。这些数据表明，Tlk家族成员在DNA复制过程中调节染色质组装，并且它们为植物杂乱突变体的多效性发育缺陷提出了合理的解释[1]。
First described in Arabidopsis thaliana [1], Tousled-like kinases (Tlks) are highly conserved in both plants and animals. in plants, Tousled kinase is essential for proper flower and leaf development, but no direct functional link to any other plant gene product has yet been established [1, 2]. Likewise, the role of Tlks in animals is unknown. In human cells, two structurally similar Tlks, Tlk1 and Tlk2, were recently shown to be cell cycle-regulated kinases with maximal activities during S phase [3]. Here, we report the identification of two human homologs of the Drosophila chromatin assembly factor Asf1 (anti-silencing function 1) [4] as physiological substrates of Tlks. We show that human Asf1 proteins are phosphorylated by Tlks both in vivo and in vitro. Furthermore, Asf1 proteins are phosphorylated during S phase, when Tlks are maximally active. Conversely, Asf1 proteins are dephosphorylated upon the activation of the DNA replication checkpoint, concomitant with the rapid inactivation of Tlks. These data indicate that Tlk family members regulate chromatin assembly during DNA replication, and they suggest a plausible explanation for the pleiotropic developmental defects of plant tousled mutants [1].