DNA topoisomerases regulate the supercoiling of nuclear DNA to influence the capacity for replication or transcription. The enzymatic function of this series of enzymes involves cutting the DNA to allow unwinding, followed by re-attachment to reseal the backbone. Members of the family are targetted in anti-cancer chemotherapy.

* Key recommended reading is highlighted with an asterisk

Alagoz M, Gilbert DC, El-Khamisy S, Chalmers AJ. (2012) DNA repair and resistance to topoisomerase I inhibitors: mechanisms, biomarkers and therapeutic targets. Curr Med Chem, 19 (23): 3874-85. [PMID:22788763]

* Baglini E, Salerno S, Barresi E, Robello M, Da Settimo F, Taliani S, Marini AM. (2021) Multiple Topoisomerase I (TopoI), Topoisomerase II (TopoII) and Tyrosyl-DNA Phosphodiesterase (TDP) inhibitors in the development of anticancer drugs. Eur J Pharm Sci, 156: 105594. [PMID:33059042]

Bansal S, Bajaj P, Pandey S, Tandon V. (2017) Topoisomerases: Resistance versus Sensitivity, How Far We Can Go?. Med Res Rev, 37 (2): 404-438. [PMID:27687257]

Baranello L, Kouzine F, Levens D. (2013) DNA topoisomerases beyond the standard role. Transcription, 4 (5): 232-7. [PMID:24135702]

* Bizard AH, Hickson ID. (2020) The many lives of type IA topoisomerases. J Biol Chem, 295 (20): 7138-7153. [PMID:32277049]

* Buzun K, Bielawska A, Bielawski K, Gornowicz A. (2020) DNA topoisomerases as molecular targets for anticancer drugs. J Enzyme Inhib Med Chem, 35 (1): 1781-1799. [PMID:32975138]

* Capranico G, Marinello J, Chillemi G. (2017) Type I DNA Topoisomerases. J Med Chem, 60 (6): 2169-2192. [PMID:28072526]

Castelli S, Coletta A, D'Annessa I, Fiorani P, Tesauro C, Desideri A. (2012) Interaction between natural compounds and human topoisomerase I. Biol Chem, 393 (11): 1327-40. [PMID:23109546]

Champoux JJ. (2001) DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem, 70: 369-413. [PMID:11395412]

Chen SH, Chan NL, Hsieh TS. (2013) New mechanistic and functional insights into DNA topoisomerases. Annu Rev Biochem, 82: 139-70. [PMID:23495937]

* Dehshahri A, Ashrafizadeh M, Ghasemipour Afshar E, Pardakhty A, Mandegary A, Mohammadinejad R, Sethi G. (2020) Topoisomerase inhibitors: Pharmacology and emerging nanoscale delivery systems. Pharmacol Res, 151: 104551. [PMID:31743776]

Gilbert DC, Chalmers AJ, El-Khamisy SF. (2012) Topoisomerase I inhibition in colorectal cancer: biomarkers and therapeutic targets. Br J Cancer, 106 (1): 18-24. [PMID:22108516]

Kathiravan MK, Khilare MM, Nikoomanesh K, Chothe AS, Jain KS. (2013) Topoisomerase as target for antibacterial and anticancer drug discovery. J Enzyme Inhib Med Chem, 28 (3): 419-35. [PMID:22380774]

Nagaraja V, Godbole AA, Henderson SR, Maxwell A. (2017) DNA topoisomerase I and DNA gyrase as targets for TB therapy. Drug Discov Today, 22 (3): 510-518. [PMID:27856347]

Pommier Y, Sun Y, Huang SN, Nitiss JL. (2016) Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. Nat Rev Mol Cell Biol, 17 (11): 703-721. [PMID:27649880]

* Riccio AA, Schellenberg MJ, Williams RS. (2020) Molecular mechanisms of topoisomerase 2 DNA-protein crosslink resolution. Cell Mol Life Sci, 77 (1): 81-91. [PMID:31728578]

Seol Y, Neuman KC. (2016) The dynamic interplay between DNA topoisomerases and DNA topology. Biophys Rev, 8 (Suppl 1): 101-111. [PMID:28510219]

Tomicic MT, Kaina B. (2013) Topoisomerase degradation, DSB repair, p53 and IAPs in cancer cell resistance to camptothecin-like topoisomerase I inhibitors. Biochim Biophys Acta, 1835 (1): 11-27. [PMID:23006513]

Węsierska-Gądek J, Składanowski A. (2012) Therapeutic intervention by the simultaneous inhibition of DNA repair and type I or type II DNA topoisomerases: one strategy, many outcomes. Future Med Chem, 4 (1): 51-72. [PMID:22168164]

1. Dodds HM, Haaz MC, Riou JF, Robert J, Rivory LP. (1998) Identification of a new metabolite of CPT-11 (irinotecan): pharmacological properties and activation to SN-38. J Pharmacol Exp Ther, 286 (1): 578-83. [PMID:9655905]

2. Drake FH, Hofmann GA, Bartus HF, Mattern MR, Crooke ST, Mirabelli CK. (1989) Biochemical and pharmacological properties of p170 and p180 forms of topoisomerase II. Biochemistry, 28 (20): 8154-60. [PMID:2557897]

3. Tanizawa A, Fujimori A, Fujimori Y, Pommier Y. (1994) Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials. J Natl Cancer Inst, 86 (11): 836-42. [PMID:8182764]