Eukaryotic DNA replication control: Lock and load, then fire
Eukaryotic DNA replication control: Lock and load, then fire
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DOI：
10.1016/j.ceb.2009.08.002
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发表时间：
2009-12-01
影响因子：
7.5
通讯作者：
Diffley, John F. X.
中科院分区：
文献类型：
--
作者：
Remus, Dirk;Diffley, John F. X.
染色体DNA复制的起始涉及在复制起点募集和装载六聚体DNA解旋酶的起始蛋白。该解旋酶加载步骤在细菌和真核生物中受到严格调控。与细菌中的情况相反，真核解旋酶以无活性形式装载。真核生物中的这种额外的“锁定和加载”机制允许调节第二步，解旋酶激活。解旋酶加载和活化的时间分离对于DNA复制与细胞生长和细胞外信号的协调、防止再复制和控制响应于复制应激的起始活性是至关重要的。细菌和真核生物中的起始蛋白在结构上是同源的，但它们所装载的复制解旋酶却不相关。了解这些解旋酶是如何加载的，以及它们在解旋过程中如何起作用，可能对理解DNA复制在不同生命领域中的调节具有重要意义。
The initiation of chromosomal DNA replication involves initiator proteins that recruit and load hexameric DNA helicases at replication origins. This helicase loading step is tightly regulated in bacteria and eukaryotes. In contrast to the situation in bacteria, the eukaryotic helicase is loaded in an inactive form. This extra 'lock and load' mechanism in eukaryotes allows regulation of a second step, helicase activation. The temporal separation of helicase loading and activation is crucial for the coordination of DNA replication with cell growth and extracellular signals, the prevention of rereplication and the control of origin activity in response to replication stress. Initiator proteins in bacteria and eukaryotes are structurally homologous; yet the replicative helicases they load are unrelated. Understanding how these helicases are loaded and how they act during unwinding may have important implications for understanding how DNA replication is regulated in different domains of life.