Cdc48 和一种泛素连接酶在 DNA 复制末期驱动 CMG 解旋酶的解体。
Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication.
机构信息
MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Cancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
出版信息
Science. 2014 Oct 24;346(6208):1253596. doi: 10.1126/science.1253596.
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 SCF(Dia2) 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.
染色体复制是由真核细胞中的一种通用机制启动的，涉及复制起点处的 CMG（Cdc45-MCM-GINS）DNA 解旋酶的组装和激活，该酶对于复制叉的推进至关重要。CMG 的解体很可能是染色体复制结束时的一个关键调控步骤，但直到现在，其机制仍不清楚。在这里，我们表明，在酿酒酵母中，已知的泛素连接酶 SCF（Dia2）在染色体复制的最后阶段促进 CMG 的泛素化。然后，Cdc48/p97 分选酶与泛素化的 CMG 结合，迅速导致解旋酶解体。这些发现表明，真核生物染色体复制的结束是以与更为复杂的起始步骤类似的复杂方式进行控制的。
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