Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, viaVenezian 1, 20133 Milan, Italy.
Curr Med Chem. 2010;17(15):1500-8. doi: 10.2174/092986710790979971.
The targeting of specific DNA repair mechanisms may be a promising strategy to improve the efficacy of antitumor therapy. The cytotoxic effects of the clinically relevant topoisomerase 1 (Top1) poison camptothecins are related to the generation of DNA lesions and tumor cells may be resistant to DNA damaging agents due to increased repair. Tyrosyl- DNA phosphodiesterase 1 (TDP1) is implicated in the repair of strand breaks by removing abortive Top1/DNA complexes. Thus, a role for TDP1 in counteracting DNA damage induced by camptothecins has been proposed. Here, we review the role of TDP1 in DNA repair with particular reference to TDP1 function, its cooperation with other pathways and the development of pharmacological inhibitors.
针对特定的 DNA 修复机制可能是提高抗肿瘤治疗效果的有前途的策略。临床上相关的拓扑异构酶 1（Top1）毒药喜树碱的细胞毒性作用与 DNA 损伤的产生有关，并且肿瘤细胞可能由于修复增加而对 DNA 损伤剂产生抗性。酪氨酰-DNA 磷酸二酯酶 1（TDP1）参与通过去除无差错的 Top1/DNA 复合物来修复链断裂。因此，已经提出了 TDP1 在抵消喜树碱诱导的 DNA 损伤中的作用。在这里，我们特别参考 TDP1 功能、与其他途径的合作以及药理学抑制剂的开发，综述了 TDP1 在 DNA 修复中的作用。
