Levels of MCM4 phosphorylation and DNA synthesis in DNA replication block checkpoint control

Levels of MCM4 phosphorylation and DNA synthesis in DNA replication block checkpoint control
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DOI:
10.1016/j.jsb.2003.11.027
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发表时间:
2004-04-01
影响因子:
3
通讯作者:
Yamada, K
Yamada, K
中科院分区:
生物学3区
文献类型:
--
作者:
Ishimi, Y;Komamura-Kohno, Y;Yamada, K

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阻断DNA复制叉的运动不仅可以稳定叉结构,而且可以阻止DNA复制的开始。我们报道了MCM4,一个假定的复制DNA解旋酶的亚基,在羟基脲(HU)存在或暴露于紫外线照射后被广泛磷酸化。在这里,我们研究了在DNA复制检查点控制期间和释放控制后MCM4磷酸化水平与DNA合成之间的关系。结果表明,这两个水平之间大致呈负相关;即MCM4磷酸化水平越高,DNA合成水平越低。HU或UV照射可刺激MCM4中几个细胞周期蛋白依赖性激酶(CDK)位点的磷酸化,从而抑制MCM4/6/7解旋酶活性。这些结果与MCM4的磷酸化在检查点控制中参与DNA合成的调控的观点是一致的。(C) 2003 Elsevier Inc.版权所有。
Blockage of a DNA replication fork movement not only stabilizes the fork structure but also prevents initiation of DNA replication. We reported that MCM4, a subunit of a putative replicative DNA helicase, is extensively phosphorylated in the presence of hydroxyurea (HU) or after exposure to UV irradiation. Here we examined the relationship between levels of MCM4 phosphorylation and DNA synthesis during DNA replication checkpoint control and after release of the control. The results suggest that there is roughly inverse correlation between these two levels; namely the higher the level of MCM4 phosphorylation, the lower the level of DNA synthesis. The presence of HU or UV irradiation can stimulate phosphorylation at several cyclin-dependent kinase (CDK) sites in MCM4, which can lead to inhibition of MCM4/6/7 helicase activity. These results are consistent with the notion that the phosphorylation of MCM4 is involved in regulation of DNA synthesis in the checkpoint control. (C) 2003 Elsevier Inc. All rights reserved.