DNA 聚合酶和 DNA 连接酶之间的相互作用：对底物通道化和 DNA 连接保真度的影响。
Interplay between DNA Polymerases and DNA Ligases: Influence on Substrate Channeling and the Fidelity of DNA Ligation.
机构信息
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
出版信息
J Mol Biol. 2019 May 17;431(11):2068-2081. doi: 10.1016/j.jmb.2019.04.028. Epub 2019 Apr 26.
Abstract
DNA ligases are a highly conserved group of nucleic acid enzymes that play an essential role in DNA repair, replication, and recombination. This review focuses on functional interaction between DNA polymerases and DNA ligases in the repair of single- and double-strand DNA breaks, and discusses the notion that the substrate channeling during DNA polymerase-mediated nucleotide insertion coupled to DNA ligation could be a mechanism to minimize the release of potentially mutagenic repair intermediates. Evidence suggesting that DNA ligases are essential for cell viability includes the fact that defects or insufficiency in DNA ligase are casually linked to genome instability. In the future, it may be possible to develop small molecule inhibitors of mammalian DNA ligases and/or their functional protein partners that potentiate the effects of chemotherapeutic compounds and improve cancer treatment outcomes.
摘要
DNA 连接酶是一类高度保守的核酸酶，在 DNA 修复、复制和重组中发挥着重要作用。本综述重点讨论了在修复单链和双链 DNA 断裂过程中 DNA 聚合酶与 DNA 连接酶之间的功能相互作用，并讨论了在 DNA 聚合酶介导的核苷酸插入与 DNA 连接偶联过程中底物通道化可能是最小化潜在诱变修复中间体释放的一种机制的观点。DNA 连接酶对于细胞活力是必需的证据包括这样一个事实，即 DNA 连接酶的缺陷或不足与基因组不稳定性有因果关系。未来，开发哺乳动物 DNA 连接酶及其功能蛋白伴侣的小分子抑制剂，可能会增强化疗药物的作用，并改善癌症治疗效果。
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