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首页> 外文期刊>Cell cycle >The DNA damage effector Chk1 kinase regulates Cdc14B nucleolar shuttling during cell cycle progression.
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The DNA damage effector Chk1 kinase regulates Cdc14B nucleolar shuttling during cell cycle progression.

机译：DNA损伤效应因子Chk1激酶在细胞周期进程中调节Cdc14B核仁穿梭。

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摘要

Chk1 is a critical effector of DNA damage checkpoints necessary for the maintenance of chromosome integrity during cell cycle progression. Here we report, that Chk1 co-localized with the nucleolar marker, fibrillarin in response to radiation-induced DNA damage in human cells. Interestingly, in vitro studies using GST pull down assays identified the dual-specificity serine/threonine nucleolar phosphatase Cdc14B as a Chk1 substrate. Furthermore, Chk1, but not a kinase-dead Chk1 control, was shown to phosphorylate Cdc14B using an in vitro kinase assay. Co-immunoprecipitation experiments using exogenous Cdc14B transfected into human cells confirmed the interaction of Cdc14B and Chk1 during cell cycle. In addition, reduction of Chk1 levels via siRNA or UCN-01 treatment demonstrated that Chk1 activation following DNA damage was required for Cdc14B export from the nucleolus. These studies have revealed a novel interplay between Chk1 kinase and Cdc14B phosphatase involving radiation-induced nucleolar shuttling to facilitate error-free cell cycle progression and prevent genomic instability.
机译：Chk1是在细胞周期进程中维持染色体完整性所必需的DNA损伤检查点的关键效应物。在这里，我们报告说，Chk1与核仁标记物原纤维蛋白共定位，以响应人类细胞中辐射诱导的DNA损伤。有趣的是，使用GST下拉检测的体外研究确定了双特异性丝氨酸/苏氨酸核仁磷酸酶Cdc14B为Chk1底物。此外，使用体外激酶测定法显示，Chk1，而不是激酶死亡的Chk1对照，磷酸化Cdc14B。使用转染到人细胞中的外源Cdc14B进行的免疫共沉淀实验证实了Cdc14B和Chk1在细胞周期中的相互作用。此外，通过siRNA或UCN-01处理降低了Chk1的水平，这表明从核仁输出Cdc14B要求DNA损伤后激活Chk1。这些研究揭示了Chk1激酶和Cdc14B磷酸酶之间的新型相互作用，涉及放射诱导的核仁穿梭，以促进无错误的细胞周期进程并防止基因组不稳定。

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