Tyrosyl-DNA phosphodiesterases: potential targets for cancer treatment
10.16438/j.0513-4870.2015-0974
- VernacularTitle:酪氨酰-DNA磷酸二酯酶:潜在的肿瘤治疗靶点
- Author:
Zhu HU
1
;
Hao-wen WANG
1
;
Lin-kun AN
1
Author Information
1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
- Publication Type:REVIEWS
- Keywords:
DNA topoisomerase;
tyrosyl-DNA phosphodiesterase;
DNA damage;
DNA end-joining repair
- From:
Acta Pharmaceutica Sinica
2016;51(2):215-
- CountryChina
- Language:Chinese
-
Abstract:
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.
