Hu Zhu, Wang Hao-wen, An Lin-kun
Yao Xue Xue Bao. 2016 Feb;51(2):215-25.
DNA topoisomerases-mediated DNA damages are generated from exogenous and endogenous effects, which need to be metabolized or repaired to maintain genome stability involving in many of repair enzymes. Tyrosyl-DNA phosphodiesterase 1(TDP1) and tyrosyl-DNA phosphodiesterase 2(TDP2) are two DNA repair enzymes discovered recently. TDP1 and TDP2 have the ability to hydrolyze the tyrosyl-phosphodiester bond of the phenol of tyrosine with 3’- and 5’-DNA end, respectively, which are contained in the metabolites of the damaged DNA mediated by topoisomerase 1 and topoisomerase 2, respectively. The abnormal activation and expression of TDP1 or TDP2 is the important reason for cancer development. Therefore, TDP1 and TDP2 have been regarded as potential targets in cancer therapy. In this review, we discuss the rationales of their potential as targets and development of their inhibitors together with topoisomerase poisons or DNA damaging agents.
DNA拓扑异构酶介导的DNA损伤由外源性和内源性作用产生，这些损伤需要代谢或修复以维持基因组稳定性，这涉及许多修复酶。酪氨酰-DNA磷酸二酯酶1（TDP1）和酪氨酰-DNA磷酸二酯酶2（TDP2）是最近发现的两种DNA修复酶。TDP1和TDP2分别具有水解酪氨酸酚与3'-和5'-DNA末端的酪氨酰-磷酸二酯键的能力，它们分别包含在拓扑异构酶1和拓扑异构酶2介导的受损DNA的代谢产物中。TDP1或TDP2的异常激活和表达是癌症发生发展的重要原因。因此，TDP1和TDP2被视为癌症治疗的潜在靶点。在这篇综述中，我们讨论了它们作为靶点的潜力的基本原理，以及它们与拓扑异构酶毒物或DNA损伤剂一起的抑制剂的开发。
