Replication stress in mammalian embryo development, differentiation, and reprogramming.
Replication stress in mammalian embryo development, differentiation, and reprogramming.
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DOI：
10.1016/j.tcb.2023.03.015
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发表时间：
2023-05
影响因子：
19
通讯作者：
Ning Wang;Shuangyi Xu;D. Egli
中科院分区：
文献类型：
--
作者：
Ning Wang;Shuangyi Xu;D. Egli
复制30亿个核苷酸的基因组受到各种障碍的挑战，这些障碍可能导致复制压力并影响基因组的完整性。近年来的研究表明，复制叉的减慢和停滞在哺乳动物的早期发育中普遍存在，导致基因组不稳定和非整倍体，并构成人类生殖发育的障碍。由DNA复制应激引起的基因组不稳定性是动物克隆和分化细胞重编程为诱导多能干细胞的障碍，也是细胞转化的障碍。值得注意的是，受复制应激影响最大的区域在这些不同的细胞环境中共享，影响长基因和侧翼基因间区域。在这篇综述中，我们整合了我们的知识，在哺乳动物胚胎中的DNA复制压力，在编程，并在重编程，我们讨论了一个潜在的作用，脆弱的网站在感知复制压力和限制细胞周期的进展，在健康和疾病。
Duplicating a genome of 3 billion nucleotides is challenged by a variety of obstacles that can cause replication stress and affect the integrity of the genome. Recent studies show that replication fork slowing and stalling is prevalent in early mammalian development, resulting in genome instability and aneuploidy, and constituting a barrier to development in human reproduction. Genome instability resulting from DNA replication stress is a barrier to the cloning of animals and to the reprogramming of differentiated cells to induced pluripotent stem cells, as well as a barrier to cell transformation. Remarkably, the regions most impacted by replication stress are shared in these different cellular contexts, affecting long genes and flanking intergenic areas. In this review we integrate our knowledge of DNA replication stress in mammalian embryos, in programming, and in reprogramming, and we discuss a potential role for fragile sites in sensing replication stress and restricting cell cycle progression in health and disease.