DNA Replication Group, Faculty of Medicine, Institute of Clinical Sciences, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
DNA Replication Group, Faculty of Medicine, Institute of Clinical Sciences, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
Semin Cell Dev Biol. 2014 Jun;30:104-9. doi: 10.1016/j.semcdb.2014.03.008. Epub 2014 Mar 14.
A central step in eukaryotic initiation of DNA replication is the loading of the helicase at replication origins, misregulation of this reaction leads to DNA damage and genome instability. Here we discuss how the helicase becomes recruited to origins and loaded into a double-hexamer around double-stranded DNA. We specifically describe the individual steps in complex assembly and explain how this process is regulated to maintain genome stability. Structural analysis of the helicase loader and the helicase has provided key insights into the process of double-hexamer formation. A structural comparison of the bacterial and eukaryotic system suggests a mechanism of helicase loading.
真核生物 DNA 复制起始的一个中心步骤是将解旋酶加载到复制原点,该反应的失调会导致 DNA 损伤和基因组不稳定。在这里,我们讨论了解旋酶如何被招募到原点并装载到双链 DNA 周围的双六聚体中。我们特别描述了复合物组装的各个步骤,并解释了如何调节这个过程以维持基因组稳定性。对解旋酶加载器和解旋酶的结构分析为双六聚体形成过程提供了重要的见解。细菌和真核系统的结构比较表明了一种解旋酶加载的机制。