Detours to Replication: Functions of Specialized DNA Polymerases during Oncogene-induced Replication Stress.
Detours to Replication: Functions of Specialized DNA Polymerases during Oncogene-induced Replication Stress.
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DOI：
10.3390/ijms19103255
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发表时间：
2018-10-20
影响因子：
5.6
通讯作者：
Eckert KA
中科院分区：
文献类型：
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作者：
Tsao WC;Eckert KA
不完整和低保真度的基因组复制有助于基因组不稳定和癌症的发展。难以复制序列（DiToRS）是基因组中的天然障碍，需要专门的DNA聚合酶和修复途径来完成和维持忠实的DNA合成。DiToRS包括由重复序列形成的非B-DNA二级结构，例如在染色体脆性位点和端粒内，其在内源性应激条件下抑制DNA复制。癌基因激活改变DNA复制动力学并产生致癌复制应激，导致DNA损伤和复制应激反应的持续激活、细胞周期停滞和细胞死亡。对致癌复制应激的反应是高度复杂的，必须严格调控以防止突变和肿瘤发生。在这篇综述中，我们总结了已知的DiToRS类型和支持复制抑制的实验证据，重点是用于科普这些障碍的专门的DNA聚合酶。此外，我们还讨论了致癌复制应激的不同原因及其对DiToRS稳定性的影响。我们强调最近的研究结果，在致癌复制压力和癌症发展的影响过程中的DNA聚合酶的调节。
Incomplete and low-fidelity genome duplication contribute to genomic instability and cancer development. Difficult-to-Replicate Sequences, or DiToRS, are natural impediments in the genome that require specialized DNA polymerases and repair pathways to complete and maintain faithful DNA synthesis. DiToRS include non B-DNA secondary structures formed by repetitive sequences, for example within chromosomal fragile sites and telomeres, which inhibit DNA replication under endogenous stress conditions. Oncogene activation alters DNA replication dynamics and creates oncogenic replication stress, resulting in persistent activation of the DNA damage and replication stress responses, cell cycle arrest, and cell death. The response to oncogenic replication stress is highly complex and must be tightly regulated to prevent mutations and tumorigenesis. In this review, we summarize types of known DiToRS and the experimental evidence supporting replication inhibition, with a focus on the specialized DNA polymerases utilized to cope with these obstacles. In addition, we discuss different causes of oncogenic replication stress and its impact on DiToRS stability. We highlight recent findings regarding the regulation of DNA polymerases during oncogenic replication stress and the implications for cancer development.
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影响因子：
64.5
作者：
Barlow JH;Faryabi RB;Callén E;Wong N;Malhowski A;Chen HT;Gutierrez-Cruz G;Sun HW;McKinnon P;Wright G;Casellas R;Robbiani DF;Staudt L;Fernandez-Capetillo O;Nussenzweig A
通讯作者：
Nussenzweig A
影响因子：
14.9
作者：
Bhat A;Andersen PL;Qin Z;Xiao W
通讯作者：
Xiao W
影响因子：
11.4
作者：
Betous, Remy;Pillaire, Marie-Jeanne;Pierini, Laura;van der Laan, Siem;Recolin, Benedicte;Ohl-Seguy, Emma;Guo, Caixia;Niimi, Naoko;Gruz, Petr;Nohmi, Takehiko;Friedberg, Errol;Cazaux, Christophe;Maiorano, Domenico;Hoffmann, Jean-Sebastien
通讯作者：
Hoffmann, Jean-Sebastien
DOI：
10.1038/nrg3296
发表时间：
2012-11
期刊：
Nature reviews. Genetics
影响因子：
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作者：
通讯作者：
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影响因子：
64.8
作者：
通讯作者：
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