Table 1.
Therapeutic and endogenous agents generating Tdp1 substrates
| Agent | Substrate(s) | Ref. |
|---|---|---|
| Reactive oxygen species | 3’ abasic site | [8-14] |
| Chain terminating nucleoside analogs1 | 3’ nucleoside adducts | [10] |
| Irradiation/Bleomycin | 3’ phospho-glycolate, 3’ abasic sites | [15-19] |
| MMS, TMZ2 | Methylated bases | [9,20] |
| PARP1 inhibitors3 | PARP1-DNA Schiff base | [21-23] |
| Camptothecins4 | 3’ phospho-tyrosine | [2,3] |
| Etoposide, doxorubicin5 | 5’ phospho-tyrosine | [20,24,25] |
| Tdp1 mutants | 3’ phospho-histidine | [1,16,26-29] |
1Arcyclovir (ACV), cytarabine (Ara-C), zidovudine (AZT), zalcitabine (ddC), and sapacitabine; 2methyl methanesulfonate (MMS) and temozolomide (TMZ); 3BMN673, Olaparib, and Rucaparip; 4U.S. Food and Drug Administration (FDA) approved analogs: topotecan and irinotecan; 5epipodophyllotoxins such as etoposide and anthracyclins, with Doxorubicin as an example, are Topo2-DNA stabilizing agents with different mechanisms of action[30]. Tdp1: Tyrosyl-DNA phosphodiesterase I