Tanaka Seiji, Tak Yon-Soo, Araki Hiroyuki
Division of Microbial Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima, Shizuoka, Japan.
Cell Div. 2007 Jun 5;2:16. doi: 10.1186/1747-1028-2-16.
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.
细胞周期蛋白依赖性激酶（CDKs）调控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，CDKs如何促进DNA复制一直是个长期存在的问题，因为DNA复制中所有必需的CDK底物尚未被鉴定出来。最近，Sld2和Sld3被鉴定为芽殖酵母DNA复制起始步骤中CDKs的必需底物。此外，绕过它们的磷酸化足以促进DNA复制。CDKs对Sld2和Sld3的磷酸化增强了与含BRCT（BRCA1 C末端）的复制蛋白Dpb11形成复合物的能力。我们进一步提出，CDKs的多重磷酸化在芽殖酵母中控制这一过程。尽管多细胞真核生物中的Sld3直系同源物尚未被鉴定出来，但真核生物中可能采用了类似的复合物形成以及因此类似的起始控制机制。
