Chromatin assembly factor 1 is essential and couples chromatin assembly to DNA replication in vivo
Chromatin assembly factor 1 is essential and couples chromatin assembly to DNA replication in vivo
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DOI：
10.1073/pnas.1635158100
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发表时间：
2003-10-14
影响因子：
11.1
通讯作者：
Stillman, B
中科院分区：
文献类型：
--
作者：
Hoek, M;Stillman, B
新生染色质组装维持复制叉后子链上的组蛋白密度。异三聚体染色质组装因子1 （caf1）在体外将DNA复制与组蛋白沉积结合在一起，但对酵母细胞增殖并不是必需的。人类细胞系中caf1的缺失表明，caf1是s期有效进展所必需的。缺乏ca -1的细胞在s期早期和中期积累，DNA复制缓慢。检查点激酶Chk1，而不是Chk2，在响应ca -1缺失时被磷酸化，这与DNA复制缺陷一致。缺乏caf1的细胞提取物完全缺乏DNA复制偶联染色质组装活性，这表明caf1是人类细胞中有效的s期进展所必需的。这些结果表明，与酵母不同，人类的CAF-1是染色质组装与DNA复制耦合所必需的。
De novo chromatin assembly maintains histone density on the daughter strands in the wake of the replication fork. The heterotrimer chromatin assembly factor 1 (CAF-1) couples DNA replication to histone deposition in vitro, but is not essential for yeast cell proliferation. Depletion of CAF-1 in human cell lines demonstrated that CAF-1 was required for efficient progression through S-phase. Cells lacking CAF-1 accumulated in early and mid S-phase and replicated DNA slowly. The checkpoint kinase Chk1, but not Chk2, was phosphorylated in response to CAF-1 depletion, consistent with a DNA replication defect. CAF-1-depleted cell extracts completely lacked DNA replication-coupled chromatin assembly activity, suggesting that CAF-1 is required for efficient S-phase progression in human cells. These results indicate that, in contrast to yeast, human CAF-1 is necessary for coupling chromatin assembly with DNA replication.