休眠起源作为真核生物DNA复制中防止基因组不稳定和疾病发展的一种内在保障。
Dormant origins as a built-in safeguard in eukaryotic DNA replication against genome instability and disease development.
作者信息
Shima Naoko, Pederson Kayla D
机构信息
The University of Minnesota, Twin Cities, Department of Genetics, Cell Biology and Development, Masonic Cancer Center, 6-160 Jackson Hall, 321 Church St SE., Minneapolis, MN 55455, United States.
The University of Minnesota, Twin Cities, Department of Genetics, Cell Biology and Development, Masonic Cancer Center, 6-160 Jackson Hall, 321 Church St SE., Minneapolis, MN 55455, United States.
出版信息
DNA Repair (Amst). 2017 Aug;56:166-173. doi: 10.1016/j.dnarep.2017.06.019. Epub 2017 Jun 9.
DNA replication is a prerequisite for cell proliferation, yet it can be increasingly challenging for a eukaryotic cell to faithfully duplicate its genome as its size and complexity expands. Dormant origins now emerge as a key component for cells to successfully accomplish such a demanding but essential task. In this perspective, we will first provide an overview of the fundamental processes eukaryotic cells have developed to regulate origin licensing and firing. With a special focus on mammalian systems, we will then highlight the role of dormant origins in preventing replication-associated genome instability and their functional interplay with proteins involved in the DNA damage repair response for tumor suppression. Lastly, deficiencies in the origin licensing machinery will be discussed in relation to their influence on stem cell maintenance and human diseases.
DNA复制是细胞增殖的前提条件，然而，随着真核细胞基因组大小和复杂性的增加，忠实地复制其基因组对细胞来说可能越来越具有挑战性。休眠起始点现已成为细胞成功完成这一艰巨但必不可少任务的关键组成部分。从这个角度来看，我们首先将概述真核细胞为调节起始点许可和激发而发展出的基本过程。特别关注哺乳动物系统，然后我们将强调休眠起始点在预防复制相关基因组不稳定中的作用，以及它们与参与肿瘤抑制的DNA损伤修复反应的蛋白质之间的功能相互作用。最后，将讨论起始点许可机制的缺陷及其对干细胞维持和人类疾病的影响。
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