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首页> 外文期刊>Molecular and Cellular Biology >Cdc6 Chromatin Affinity Is Unaffected by Serine-54 Phosphorylation, S-Phase Progression, and Overexpression of Cyclin A
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Cdc6 Chromatin Affinity Is Unaffected by Serine-54 Phosphorylation, S-Phase Progression, and Overexpression of Cyclin A

机译：Cdc6染色质亲和力不受丝氨酸54磷酸化，S相进程和细胞周期蛋白A过表达的影响

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Ectopically expressed Cdc6 is translocated from the nucleus during S phase in a cyclin A-Cdk2-dependent process, suggesting that reinitiation of DNA replication is prevented by removal of phosphorylated Cdc6 from chromatin after origin firing. However, whether endogenous Cdc6 translocates during S phase remains controversial. To resolve the questions regarding regulation of endogenous Cdc6, we cloned the cDNA encoding the Chinese hamster Cdc6 homolog and specifically focused on analyzing the localizations and chromatin affinities of endogenous and exogenous proteins during S phase and following overexpression of cyclin A. In agreement with other reports, ectopically expressed Cdc6 translocates from the nucleus during S phase and in response to overexpressed cyclin A. In contrast, using a combination of biochemical and immunohistochemical assays, we show convincingly that endogenous Cdc6 remains nuclear and chromatin bound throughout the entire S period, while Mcm5 loses chromatin affinity during S phase. Overexpression of cyclin A is unable to alter the nuclear localization of Cdc6. Furthermore, using a phosphospecific antibody we show that phosphoserine-54 Cdc6 maintains a high affinity for chromatin during the S period. Considering recent in vitro studies, these data are consistent with a proposed model in which Cdc6 is serine-54 phosphorylated during S phase and functions as a chromatin-bound signal that prevents reformation of prereplication complexes.
机译：异位表达的Cdc6在细胞周期蛋白A-Cdk2依赖性过程中的S期从细胞核移位，这表明通过在原始激发后从染色质中去除磷酸化的Cdc6，可以防止DNA复制的重新初始化。但是，内源性Cdc6在S期是否易位仍存在争议。为了解决有关内源性Cdc6调控的问题，我们克隆了编码中国仓鼠Cdc6同源物的cDNA，特别侧重于分析S期以及细胞周期蛋白A过表达后内源性和外源性蛋白的定位和染色质亲和力。与其他报道一致，异位表达的Cdc6在S期和响应过表达的细胞周期蛋白A时从细胞核移位。相反，使用生物化学和免疫组化方法的组合，我们令人信服地表明，内源性Cdc6在整个S时期仍保持核和染色质结合，而Mcm5在S期失去染色质亲和力细胞周期蛋白A的过表达不能改变Cdc6的核定位。此外，使用磷酸化特异性抗体，我们证明了磷酸丝氨酸54 Cdc6在S期对染色质保持高亲和力。考虑到最近的体外研究，这些数据与提出的模型一致，在该模型中，Cdc6在S期被丝氨酸54磷酸化，并作为染色质结合信号起作用，阻止了复制前复合物的重新形成。

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