Distinct roles for Sld3 and GINS during establishment and progression of eukaryotic DNA replication forks
Distinct roles for Sld3 and GINS during establishment and progression of eukaryotic DNA replication forks
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DOI：
10.1038/sj.emboj.7601063
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发表时间：
2006-04-19
期刊：
影响因子：
11.4
通讯作者：
Labib, Karim
中科院分区：
文献类型：
--
作者：
Kanemaki, Masato;Labib, Karim
Cdc 45蛋白对于真核细胞中染色体复制的起始是至关重要的，因为它允许激活含有MCM解旋酶的复制前复合物（pre-RC）。这导致了起始点的解旋和DNA复制叉的建立。Cdc 45在新生分叉处的掺入是一个高度调节且知之甚少的过程，其在芽殖酵母中需要Sld 3蛋白和GINS复合物。以前的研究表明，Sld 3在起始步骤后对DNA复制叉的进展也很重要，Cdc 45和GINS也是如此。相比之下，我们在这里表明，Sld 3不移动与DNA复制叉，只与MCM在一个不稳定的方式开始之前。在从早期起源建立DNA复制叉后，Sld 3不再是完成染色体复制所必需的。与Sld 3不同，GINS不是Cdc 45最初募集到起源所必需的，而是Cdc 45与新生复制体稳定接合所必需的。与Cdc 45一样，GINS在S期与MCM稳定缔合。
The Cdc45 protein is crucial for the initiation of chromosome replication in eukaryotic cells, as it allows the activation of prereplication complexes (pre-RCs) that contain the MCM helicase. This causes the unwinding of origins and the establishment of DNA replication forks. The incorporation of Cdc45 at nascent forks is a highly regulated and poorly understood process that requires, in budding yeast, the Sld3 protein and the GINS complex. Previous studies suggested that Sld3 is also important for the progression of DNA replication forks after the initiation step, as are Cdc45 and GINS. In contrast, we show here that Sld3 does not move with DNA replication forks and only associates with MCM in an unstable manner before initiation. After the establishment of DNA replication forks from early origins, Sld3 is no longer essential for the completion of chromosome replication. Unlike Sld3, GINS is not required for the initial recruitment of Cdc45 to origins and instead is necessary for stable engagement of Cdc45 with the nascent replisome. Like Cdc45, GINS then associates stably with MCM during S-phase.