The role of CDK in the initiation step of DNA replication in eukaryotes.

The role of CDK in the initiation step of DNA replication in eukaryotes.
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DOI:
10.1186/1747-1028-2-16
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发表时间:
2007-06-05
期刊:
影响因子:
2.3
通讯作者:
Araki H
Araki H
中科院分区:
生物学3区
文献类型:
--
作者:
Tanaka S;Tak YS;Araki H

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细胞周期蛋白依赖性激酶(CDK)调节真核生物细胞周期的进程。CDK的主要作用之一是促进染色体DNA复制。然而,CDK如何促进DNA复制一直是一个长期存在的问题,因为DNA复制中所有必需的CDK底物尚未被确定。最近,Sld 2和Sld 3被鉴定为芽殖酵母中DNA复制起始步骤中CDK的必需底物。此外,绕过它们的磷酸化足以促进DNA复制。通过CDK磷酸化Sld 2和Sld 3增强与含有BRCT(BRCA 1 C-末端)的复制蛋白Dpb 11的复合物的形成。我们进一步提出,在芽殖酵母中,CDKs的多重磷酸化控制着这一过程。即使Sld 3直向同源物在多细胞真核生物中尚未被确定,类似的复合物的形成,因此,类似的启动控制机制可能会在真核生物中使用。
Cyclin-dependent kinases (CDKs) regulate the progression of the cell cycle in eukaryotes. One of the major roles of CDK is to promote chromosomal DNA replication. However, how CDKs promote DNA replication has been a long-standing question, because all the essential CDK substrates in DNA replication have not been identified yet. Recently Sld2 and Sld3 were identified as essential substrates of CDKs in the initiation step of DNA replication in budding yeast. Moreover, bypass of their phosphorylations is sufficient to promote DNA replication. Phosphorylation of Sld2 and Sld3 by CDKs enhances the formation of complex(es) with a BRCT (BRCA1 C-Terminal)-containing replication protein, Dpb11. We further propose that multiple phosphorylation by CDKs controls this process in budding yeast. Even though Sld3 orthologues in multicellular eukaryotes have not been identified, similar complex formation and, therefore, a similar mechanism of initiation control might be employed in eukaryotes.
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