Regulation of DNA Replication through Natural Impediments in the Eukaryotic Genome.
Regulation of DNA Replication through Natural Impediments in the Eukaryotic Genome.
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DOI：
10.3390/genes8030098
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发表时间：
2017-03-07
期刊：
影响因子：
3.5
通讯作者：
Noguchi E
中科院分区：
文献类型：
--
作者：
Gadaleta MC;Noguchi E
所有活着的有机体都需要复制它们的遗传信息，同时保护它们免受不必要的突变的影响，这些突变可能会导致遗传疾病和癌症的发展。DNA复制过程中的不准确是基因组不稳定的主要原因，因为复制叉容易停滞和坍塌，导致DNA损伤。外源DNA损伤剂的存在以及含有DNA-蛋白质复合体、重复DNA、二级DNA结构或转录RNA聚合酶的内源难以复制的DNA区域的存在，增加了基因组不稳定的风险，从而威胁到细胞的生存。因此，了解在S阶段保存遗传信息所需的细胞机制是至关重要的。在这篇综述中，我们将讨论我们目前对细胞如何应对这些自然障碍的理解，以防止DNA损伤和DNA复制过程中的基因组不稳定。
All living organisms need to duplicate their genetic information while protecting it from unwanted mutations, which can lead to genetic disorders and cancer development. Inaccuracies during DNA replication are the major cause of genomic instability, as replication forks are prone to stalling and collapse, resulting in DNA damage. The presence of exogenous DNA damaging agents as well as endogenous difficult-to-replicate DNA regions containing DNA–protein complexes, repetitive DNA, secondary DNA structures, or transcribing RNA polymerases, increases the risk of genomic instability and thus threatens cell survival. Therefore, understanding the cellular mechanisms required to preserve the genetic information during S phase is of paramount importance. In this review, we will discuss our current understanding of how cells cope with these natural impediments in order to prevent DNA damage and genomic instability during DNA replication.