Institute of Human Genetics, CNRS-UPR1142, Department "Molecular Bases of Human Diseases", 141, Rue de la Cardonille, Montpellier 34396 Cedex 5, France.
RNA Biogenesis Laboratory, Institute of Molecular Genetics of Montpellier, 1919 Route de Mende, Montpellier 34293, France.
Genes (Basel). 2014 Mar 6;5(1):147-75. doi: 10.3390/genes5010147.
The major challenge of the cell cycle is to deliver an intact, and fully duplicated, genetic material to the daughter cells. To this end, progression of DNA synthesis is monitored by a feedback mechanism known as replication checkpoint that is untimely linked to DNA replication. This signaling pathway ensures coordination of DNA synthesis with cell cycle progression. Failure to activate this checkpoint in response to perturbation of DNA synthesis (replication stress) results in forced cell division leading to chromosome fragmentation, aneuploidy, and genomic instability. In this review, we will describe current knowledge of the molecular determinants of the DNA replication checkpoint in eukaryotic cells and discuss a model of activation of this signaling pathway crucial for maintenance of genomic stability.
细胞周期的主要挑战是将完整且完全复制的遗传物质传递给子细胞。为此，通过一种称为复制检查点的反馈机制来监测 DNA 合成的进展，该机制与 DNA 复制的时间不当相关联。该信号通路确保了 DNA 合成与细胞周期进程的协调。如果不能及时激活该检查点以响应 DNA 合成的扰动（复制应激），则会导致强制细胞分裂，导致染色体碎片化、非整倍体和基因组不稳定。在这篇综述中，我们将描述真核细胞中 DNA 复制检查点的分子决定因素的最新知识，并讨论该信号通路的激活模型，这对于维持基因组稳定性至关重要。
