Naruyama Hiromichi, Shimada Midori, Niida Hiroyuki, Zineldeen Doaa H, Hashimoto Yoshihiro, Kohri Kenjiro, Nakanishi Makoto
Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Biochem Biophys Res Commun. 2008 Sep 12;374(1):79-83. doi: 10.1016/j.bbrc.2008.06.112. Epub 2008 Jul 9.
Chk1 is an essential kinase for maintaining genome integrity and cell cycle checkpoints through phosphorylating several downstream targets. Recently, we demonstrated that Chk1 is also required for cell proliferation in somatic cells under unperturbed condition through regulating transcription of several genes. Here, we show that Chk1 is required for S phase progression and RNR2 is a critical downstream target of genes transcriptionally regulated by Chk1. Hence, although RNR2 expression reached maximum at S phase in the presence of Chk1, Chk1 depletion arrested the cell cycle at S phase and reduced RNR2 expression at both mRNA and protein levels. Ectopic expression of RNR2 failed to rescue the S phase arrest observed in Chk1 depleted cells, suggesting the presence of an additional Chk1-target(s) for completion of S phase other than RNR2. Therefore, our results suggest that Chk1 is required for DNA replication at least through regulating RNR2 gene transcription.
Chk1是一种重要的激酶，通过磷酸化多个下游靶点来维持基因组完整性和细胞周期检查点。最近，我们证明Chk1在未受干扰的条件下，通过调节多个基因的转录，对体细胞的细胞增殖也是必需的。在这里，我们表明Chk1是S期进展所必需的，而RNR2是受Chk1转录调控的关键下游靶点。因此，尽管在Chk1存在的情况下RNR2表达在S期达到最大值，但Chk1的缺失使细胞周期停滞在S期，并在mRNA和蛋白质水平上降低了RNR2的表达。RNR2的异位表达未能挽救在Chk1缺失细胞中观察到的S期停滞，这表明除了RNR2之外，还存在其他Chk1靶点来完成S期。因此，我们的结果表明Chk1至少通过调节RNR2基因转录对DNA复制是必需的。
