The role of the Saccharomyces cerevisiae Cdc7-Dbf4 complex in the replication checkpoint
The role of the Saccharomyces cerevisiae Cdc7-Dbf4 complex in the replication checkpoint
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DOI：
10.1016/j.gene.2008.02.010
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发表时间：
2008-05-15
期刊：
影响因子：
3.5
通讯作者：
Masumoto, Hiroshi
中科院分区：
文献类型：
--
作者：
Ogi, Hiroo;Wang, Cheng-Zhong;Masumoto, Hiroshi
Cdc 7-Dbf 4复合物是一种保守的丝氨酸/苏氨酸蛋白激酶，对真核DNA复制的起始至关重要。尽管mcm 5-bob 1突变绕过了由CDC 7或DBF 4中的突变所赋予的致死性，但Delta cdc 7 mcm 5-bob 1突变体对诱导复制应激的羟基脲（H-U）敏感。为了阐明缺失CDC 7所赋予的HU敏感性的原因，我们研究了Cdc 7-Dbf 4在复制检查点中的作用。我们发现，在Cdc 7-Dbf 4缺陷细胞暴露于复制应激，Rad 53仍然在hypophosphorylated形式，后期纺锤体被拉长，检查点特异性转录不诱导。低磷酸化的Rad 53表现出低的自磷酸化活性，并且重组Cdc 7-Dbf 4在体外磷酸化Rad 53。这些结果表明，Cdc 7-Dbf 4是需要的Rad 53在复制应激反应的完全激活。(c)2008 Elsevier B. V.保留所有权利。
The Cdc7-Dbf4 complex is a conserved serine/threonine protein kinase essential for the initiation of eukaryotic DNA replication. Although an mcm5-bob1 mutation bypasses lethality conferred by mutations in CDC7 or DBF4, the Delta cdc7 mcm5-bob1 mutant is sensitive to hydroxyurea (H-U), which induces replication stress. To elucidate the reasons for HU sensitivity conferred by deletion of CDC7, we examined the role of Cdc7-Dbf4 in the replication checkpoint. We found that in Cdc7-Dbf4-deficient cells exposed to replication stress, Rad53 remains in a hypophosphorylated form, anaphase spindle is elongated, and checkpoint-specific transcription is not induced. The hypophosphorylated Rad53 exhibits a low autophosphorylation activity, and recombinant Cdc7-Dbf4 phosphorylates Rad53 in vitro. These results suggest that Cdc7-Dbf4 is required for full activation of Rad53 in response to replication stress. (c) 2008 Elsevier B.V. All rights reserved.