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Cdk1 Regulates the Temporal Recruitment of Telomerase and Cdc13-Stn1-Ten1 Complex for Telomere Replication

机译:Cdk1调节端粒酶和Cdc13-Stn1-Ten1复杂的端粒复制的时间招募。

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In budding yeast (Saccharomyces cerevisiae), the cell cycle-dependent telomere elongation by telomerase is controlled by the cyclin-dependent kinase 1 (Cdk1). The telomere length homeostasis is balanced between telomerase-unextendable and telomerase-extendable states that both require Cdc13. The recruitment of telomerase complex by Cdc13 promotes telomere elongation, while the formation of Cdc13-Stn1-Ten1 (CST) complex at the telomere blocks telomere elongation by telomerase. However, the cellular signaling that regulates the timing of the telomerase-extendable and telomerase-unextendable states is largely unknown. Phosphorylation of Cdc13 by Cdk1 promotes the interaction between Cdc13 and Est1 and hence telomere elongation. Here, we show that Cdk1 also phosphorylates Stn1 at threonine 223 and serine 250 both in vitro and in vivo, and these phosphorylation events are essential for the stability of the CST complexes at the telomeres. By controlling the timing of Cdc13 and Stn1 phosphorylations during cell cycle progression, Cdk1 regulates the temporal recruitment of telomerase complexes and CST complexes to the telomeres to facilitate telomere maintenance.
机译:在出芽的酵母中(Saccharomyces cerevisiae),端粒酶的细胞周期依赖性端粒伸长受细胞周期蛋白依赖性激酶1(Cdk1)的控制。端粒长度动态平衡在都需要Cdc13的端粒酶不可扩展状态和端粒酶可扩展状态之间达到平衡。 Cdc13募集端粒酶复合物可促进端粒伸长,而在端粒上形成Cdc13-Stn1-Ten1(CST)复合物可阻止端粒酶通过端粒伸长。然而,调节端粒酶可扩展和端粒酶不可扩展状态的时间的细胞信号传导在很大程度上是未知的。 Cdk1对Cdc13的磷酸化促进了Cdc13与Est1之间的相互作用,从而促进了端粒的延长。在这里,我们显示Cdk1还可以在体外和在体内将苏氨酸223和丝氨酸250上的Stn1磷酸化,并且这些磷酸化事件对于CST复合物的稳定性至关重要。端粒。通过控制细胞周期进程中Cdc13和Stn1磷酸化的时间,Cdk1调节端粒酶复合物和CST复合物到端粒的时间募集,以促进端粒的维持。

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