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首页> 外文期刊>Genes to cells : >Control of DNA replication licensing in a cell cycle.
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Control of DNA replication licensing in a cell cycle.

机译：在细胞周期内控制DNA复制许可。

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To maintain genome integrity in eukaryotes, DNA must be duplicated precisely once before cell division occurs. A process called replication licensing ensures that chromosomes are replicated only once per cell cycle. Its control has been uncovered by the discovery of the CDKs (cyclin dependent kinases) as master regulators of the cell cycle and the initiator proteins of DNA replication, such as the Origin Recognition Complex (ORC), Cdc6/18, Cdt1 and the MCM complex. At the end of mitosis, the MCM complex is loaded on to chromatin with the aid of ORC, Cdc6/18 and Cdt1, and chromatin becomes licensed for replication. CDKs, together with the Cdc7 kinase, trigger the initiation of replication, recruiting the DNA replicating enzymes on sites of replication. The activated MCM complex appears to play a key role in the DNA unwinding step, acting as a replicating helicase and moves along with the replication fork, at the same time bringing the origins to the unlicensed state. The cycling of CDK activity in the cell cycle separates the two states of replication origins, the licensed state in G1-phase and the unlicensed state for the rest of the cell cycle. Only when CDK drops at the completion of mitosis, is the restriction on licensing relieved and a new round of replication is allowed. Such a CDK-regulated licensing control is conserved from yeast to higher eukaryotes, and ensures that DNA replication takes place only once in a cycle. Xenopus laevis and mammalian cells have an additional system to control licensing. Geminin, whose degradation at the end of mitosis is essential for a new round of licensing, has been shown to bind Cdt1 and negatively regulate it, providing a new insight into the regulation of DNA replication in higher eukaryotes.
机译：为了维持真核生物中的基因组完整性，必须在细胞分裂发生之前将DNA精确复制一次。一种称为复制许可的过程可确保每个细胞周期仅复制一次染色体。通过发现CDK（细胞周期蛋白依赖性激酶）作为细胞周期的主要调节剂和DNA复制的起始蛋白（例如起源识别复合物（ORC），Cdc6 / 18，Cdt1和MCM复合物），发现了其控制作用。 。在有丝分裂结束时，借助ORC，Cdc6 / 18和Cdt1将MCM复合物加载到染色质上，然后染色质获得复制许可。 CDK与Cdc7激酶一起触发复制的启动，在复制位点募集DNA复制酶。活化的MCM复合物似乎在DNA展开步骤中起关键作用，充当复制解旋酶并与复制叉一起移动，同时将来源变为未许可状态。 CDK活性在细胞周期中的循环将复制起点的两个状态分开，即G1期的许可状态和其余细胞周期的非许可状态。只有在有丝分裂完成时CDK下降时，才可以解除对许可的限制，并允许进行新的复制。这样的CDK调控的许可控制从酵母到高级真核生物都是保守的，并确保DNA复制仅在一个周期中发生一次。非洲爪蟾和哺乳动物细胞还有一个额外的系统来控制许可。 Geminin在有丝分裂结束时的降解对于新一轮许可至关重要，已显示出结合Cdt1并对其负调控，从而为高级真核生物中DNA复制的调控提供了新的见识。

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