Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication.

Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication.
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DOI:
10.1126/science.1253596
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发表时间:
2014-10-24
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Labib K
Labib K
中科院分区:
其他
文献类型:
--
作者:
Maric M;Maculins T;De Piccoli G;Labib K

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真核细胞中的染色体复制是由一种普遍的机制启动的,它涉及CMG(CDC45-MCM-GINS)DNA解旋酶在复制起始处的组装和激活,它是复制叉前进所必需的。CMG的解离很可能是染色体复制结束时的一个关键调控步骤,但其机制至今尚不清楚。在这里,我们发现在酿酒酵母染色体复制的最后阶段,被称为SCFDia2的泛素连接酶促进CMG泛素化。然后CDC48/p97分离酶与泛素化的CMG结合,导致解旋酶的快速分解。这些发现表明,真核生物中染色体复制的结束受到类似于特征更好的起始步骤的复杂方式的控制。
Chromosome replication is initiated by a universal mechanism in eukaryotic cells, involving the assembly and activation at replication origins of the CMG (Cdc45-MCM-GINS) DNA helicase, which is essential for the progression of replication forks. Disassembly of CMG is likely to be a key regulated step at the end of chromosome replication, but the mechanism was unknown until now. Here we show that the ubiquitin ligase known as SCFDia2 promotes ubiquitylation of CMG during the final stages of chromosome replication in Saccharomyces cerevisiae. The Cdc48/p97 segregase then associates with ubiquitylated CMG, leading rapidly to helicase disassembly. These findings indicate that the end of chromosome replication in eukaryotes is controlled in a similarly complex fashion to the much-better-characterized initiation step.
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