GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks
GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks
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DOI：
10.1038/ncb1382
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发表时间：
2006-04-01
影响因子：
21.3
通讯作者：
Labib, K
中科院分区：
文献类型：
--
作者：
Gambus, A;Jones, RC;Labib, K
通过控制真核生物DNA复制叉的进展来保持基因组稳定性的复制体的组成部分尚不清楚。在这里，我们发现GINS （go ichi ni san）复合体允许MCM（小染色体维持）解旋酶与大型复制体进展复合体（rpc）中的关键调节蛋白相互作用，这些复合体在起始阶段组装并在S期结束时拆卸。RPC组分包括必需的起始和延伸因子，Cdc45，检查点介质Mrc1，允许复制叉在蛋白质- DNA屏障处暂停的Tof1 - Csm3复合物，组蛋白伴侣蛋白FACT（促进染色质转录）和Ctf4，它有助于建立姐妹染色单体内聚。RPC还与Mcm10和拓扑异构酶i相互作用。在起始过程中，GINS对于RPC蛋白的特定子集与MCM相互作用至关重要。GINS对于DNA复制分叉的正常进程也很重要，我们发现在启动后需要它来维持RPCs中MCM和Cdc45之间的关联。
The components of the replisome that preserve genomic stability by controlling the progression of eukaryotic DNA replication forks are poorly understood. Here, we show that the GINS ( go ichi ni san) complex allows the MCM ( minichromosome maintenance) helicase to interact with key regulatory proteins in large replisome progression complexes (RPCs) that are assembled during initiation and disassembled at the end of S phase. RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1 - Csm3 complex that allows replication forks to pause at protein - DNA barriers, the histone chaperone FACT ( facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion. RPCs also interact with Mcm10 and topoisomerase I. During initiation, GINS is essential for a specific subset of RPC proteins to interact with MCM. GINS is also important for the normal progression of DNA replication forks, and we show that it is required after initiation to maintain the association between MCM and Cdc45 within RPCs.