DNA replication stress: oncogenes in the spotlight
DNA replication stress: oncogenes in the spotlight
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DOI：
10.1590/1678-4685gmb-2019-0138
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发表时间：
2020-01-01
影响因子：
2.1
通讯作者：
Teixeira, Leonardo K.
中科院分区：
文献类型：
--
作者：
Primo, Luiza M. F.;Teixeira, Leonardo K.
遗传物质的精确复制对维持基因组稳定性至关重要。DNA复制是一个严格调控的过程，在每个细胞周期中将DNA分子的忠实拷贝复制到子细胞。DNA复制的扰动可能损害遗传信息的传递，导致DNA损伤、突变和染色体重排。DNA复制应激，也被称为DNA复制应激，被定义为在DNA合成期间由于不同的损伤而导致的复制叉进展的减慢或停滞。癌基因激活是癌症的一个标志，能够干扰许多细胞过程，包括DNA复制。事实上，大量的研究表明，癌基因诱导的复制应激是人类致癌过程中基因组不稳定性的重要来源。在这篇综述中，我们重点介绍了诱导DNA复制应激的主要癌基因，例如RAS、MYC、Cyclin E、MDM 2和BCL-2等，以及这些癌基因干扰正常DNA复制并促进基因组不稳定性的分子机制。
Precise replication of genetic material is essential to maintain genome stability. DNA replication is a tightly regulated process that ensues faithful copies of DNA molecules to daughter cells during each cell cycle. Perturbation of DNA replication may compromise the transmission of genetic information, leading to DNA damage, mutations, and chromosomal rearrangements. DNA replication stress, also referred to as DNA replicative stress, is defined as the slowing or stalling of replication fork progression during DNA synthesis as a result of different insults. Oncogene activation, one hallmark of cancer, is able to disturb numerous cellular processes, including DNA replication. In fact, extensive work has indicated that oncogene-induced replication stress is an important source of genomic instability in human carcinogenesis. In this review, we focus on main oncogenes that induce DNA replication stress, such as RAS, MYC, Cyclin E, MDM2, and BCL-2 among others, and the molecular mechanisms by which these oncogenes interfere with normal DNA replication and promote genomic instability.