DNA Polymerases at the Eukaryotic Replication Fork Thirty Years after: Connection to Cancer.
DNA Polymerases at the Eukaryotic Replication Fork Thirty Years after: Connection to Cancer.
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DOI：
10.3390/cancers12123489
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发表时间：
2020-11-24
期刊：
影响因子：
5.2
通讯作者：
Stepchenkova EI
中科院分区：
文献类型：
--
作者：
Pavlov YI;Zhuk AS;Stepchenkova EI
癌症的病因与遗传物质复制过程中发生的突变有关。导致低复制保真度的突变是许多遗传性和散发性癌症的罪魁祸首。当前复制分叉模型的原型是在30年前提出的。在我们2010年的评论的续集中，受A. Dumas小说的启发，标题中有“多年之后”的词，我们回顾了DNA复制领域的新发展，并分析了它们如何帮助阐明DNA聚合酶的遗传变异对癌症的影响。最近对肿瘤基因组的研究表明，复制DNA聚合酶基因的突变通过增加基因组的不稳定性导致癌症易感性。在过去的10年里，人们发现了关于复制DNA聚合酶的结构和功能以及复制叉组织的令人兴奋的细节。Morrison及其合作者在30年前提出的不同聚合酶参与分叉处特定交易的主要观点（后来被命名为“劳动分工”）仍然存在，并对聚合酶δ在滞后和前导DNA链复制中的更广泛作用进行了修正。然而，癌症相关突变主要影响参与前导链DNA合成的聚合酶ε的催化亚基。我们分析了DNA复制领域的新发现如何帮助阐明聚合酶变异对癌症的影响。
The etiology of cancer is linked to the occurrence of mutations during the reduplication of genetic material. Mutations leading to low replication fidelity are the culprits of many hereditary and sporadic cancers. The archetype of the current model of replication fork was proposed 30 years ago. In the sequel to our 2010 review with the words “years after” in the title inspired by A. Dumas’s novels, we go over new developments in the DNA replication field and analyze how they help elucidate the effects of the genetic variants of DNA polymerases on cancer. Recent studies on tumor genomes revealed that mutations in genes of replicative DNA polymerases cause a predisposition for cancer by increasing genome instability. The past 10 years have uncovered exciting details about the structure and function of replicative DNA polymerases and the replication fork organization. The principal idea of participation of different polymerases in specific transactions at the fork proposed by Morrison and coauthors 30 years ago and later named “division of labor,” remains standing, with an amendment of the broader role of polymerase δ in the replication of both the lagging and leading DNA strands. However, cancer-associated mutations predominantly affect the catalytic subunit of polymerase ε that participates in leading strand DNA synthesis. We analyze how new findings in the DNA replication field help elucidate the polymerase variants’ effects on cancer.
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影响因子：
16
作者：
Bellelli R;Borel V;Logan C;Svendsen J;Cox DE;Nye E;Metcalfe K;O'Connell SM;Stamp G;Flynn HR;Snijders AP;Lassailly F;Jackson A;Boulton SJ
通讯作者：
Boulton SJ
影响因子：
64.8
作者：
BRONNER, CE;BAKER, SM;LISKAY, RM
通讯作者：
LISKAY, RM
影响因子：
4.3
作者：
Becker, Jordan R.;Hai Dang Nguyen;Bielinsky, Anja-Katrin
通讯作者：
Bielinsky, Anja-Katrin
影响因子：
3.5
作者：
Church DN;Briggs SE;Palles C;Domingo E;Kearsey SJ;Grimes JM;Gorman M;Martin L;Howarth KM;Hodgson SV;NSECG Collaborators;Kaur K;Taylor J;Tomlinson IP
通讯作者：
Tomlinson IP
影响因子：
16.6
作者：
Burgers PMJ;Kunkel TA
通讯作者：
Kunkel TA