Pavlov Youri I, Zhuk Anna S, Stepchenkova Elena I
Eppley Institute for Research in Cancer and Allied Diseases and Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Genetics and Biotechnology, Saint-Petersburg State University, 199034 Saint Petersburg, Russia.
Cancers (Basel). 2020 Nov 24;12(12):3489. doi: 10.3390/cancers12123489.
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.
近期对肿瘤基因组的研究表明，复制性DNA聚合酶基因的突变会因增加基因组不稳定性而导致患癌倾向。在过去十年中，人们发现了有关复制性DNA聚合酶的结构与功能以及复制叉组织的一些令人兴奋的细节。30年前莫里森及其合著者提出的不同聚合酶参与复制叉特定过程的主要观点（后来被称为“分工”）仍然成立，不过现在对聚合酶δ在滞后链和前导链DNA复制中的更广泛作用有了修正。然而，与癌症相关的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有助于阐明聚合酶变体对癌症的影响。
