Hernández-Carralero Esperanza, Cabrera Elisa, Alonso-de Vega Ignacio, Hernández-Pérez Santiago, Smits Veronique A J, Freire Raimundo
Unidad de Investigación, Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas, Ofra s/n, 38320 La Laguna, Tenerife, Spain.
Division of Oncogenomics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Cells. 2018 Sep 20;7(10):146. doi: 10.3390/cells7100146.
Eukaryotic cells divide by accomplishing a program of events in which the replication of the genome is a fundamental part. To ensure all cells have an accurate copy of the genome, DNA replication occurs only once per cell cycle and is controlled by numerous pathways. A key step in this process is the initiation of DNA replication in which certain regions of DNA are marked as competent to replicate. Moreover, initiation of DNA replication needs to be coordinated with other cell cycle processes. At the molecular level, initiation of DNA replication relies, among other mechanisms, upon post-translational modifications, including the conjugation and hydrolysis of ubiquitin. An example is the precise control of the levels of the DNA replication initiation protein Cdt1 and its inhibitor Geminin by ubiquitin-mediated proteasomal degradation. This control ensures that DNA replication occurs with the right timing during the cell cycle, thereby avoiding re-replication events. Here, we review the events that involve ubiquitin signalling during DNA replication initiation, and how they are linked to human disease.
真核细胞通过完成一系列事件来进行分裂，其中基因组的复制是一个基本部分。为确保所有细胞都有基因组的精确拷贝，DNA复制在每个细胞周期中仅发生一次，并受众多途径控制。这一过程中的一个关键步骤是DNA复制的起始，其中DNA的某些区域被标记为有能力进行复制。此外，DNA复制的起始需要与其他细胞周期过程相协调。在分子水平上，DNA复制的起始除其他机制外，还依赖于翻译后修饰，包括泛素的结合和水解。一个例子是通过泛素介导的蛋白酶体降解精确控制DNA复制起始蛋白Cdt1及其抑制剂Geminin的水平。这种控制确保DNA复制在细胞周期的正确时间发生，从而避免重新复制事件。在这里，我们综述了DNA复制起始过程中涉及泛素信号传导的事件，以及它们与人类疾病的联系。
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