TDP1

Summary

Gene Symbol: TDP1
Description: tyrosyl-DNA phosphodiesterase 1
Alias: tyrosyl-DNA phosphodiesterase 1, tyr-DNA phosphodiesterase 1
Species: human
Products:     TDP1

Top Publications

  1. Raymond A, Staker B, Burgin A. Substrate specificity of tyrosyl-DNA phosphodiesterase I (Tdp1). J Biol Chem. 2005;280:22029-35 pubmed
    Tyrosyl-DNA phosphodiesterase I (Tdp1) hydrolyzes 3'-phosphotyrosyl bonds to generate 3'-phosphate DNA and tyrosine in vitro...
  2. Davies D, Interthal H, Champoux J, Hol W. The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1. Structure. 2002;10:237-48 pubmed
    Tyrosyl-DNA phosphodiesterase (Tdp1) catalyzes the hydrolysis of a phosphodiester bond between a tyrosine residue and a DNA 3' phosphate...
  3. Lebedeva N, Rechkunova N, Lavrik O. AP-site cleavage activity of tyrosyl-DNA phosphodiesterase 1. FEBS Lett. 2011;585:683-6 pubmed publisher
    ..In this study it has been found that recently discovered tyrosyl-DNA phosphodiesterase 1 (Tdp1) catalyzes the AP site cleavage reaction to generate breaks with the 3'- and 5'-phosphate termini...
  4. Inamdar K, Pouliot J, Zhou T, Lees Miller S, Rasouli Nia A, Povirk L. Conversion of phosphoglycolate to phosphate termini on 3' overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1. J Biol Chem. 2002;277:27162-8 pubmed
    ..Recombinant hTdp1, as well as Saccharomyces cerevisiae Tdp1, catalyzed similar removal of glycolate, although less efficiently than removal of tyrosine...
  5. El Khamisy S, Hartsuiker E, Caldecott K. TDP1 facilitates repair of ionizing radiation-induced DNA single-strand breaks. DNA Repair (Amst). 2007;6:1485-95 pubmed
    Tyrosyl DNA phosphodiesterase-1 (TDP1) is the gene product mutated in spinocerebellar ataxia with axonal neuropathy1 (SCAN1)...
  6. Dexheimer T, Stephen A, Fivash M, Fisher R, Pommier Y. The DNA binding and 3'-end preferential activity of human tyrosyl-DNA phosphodiesterase. Nucleic Acids Res. 2010;38:2444-52 pubmed publisher
    Human tyrosyl-DNA phosphodiesterase (Tdp1) processes 3'-blocking lesions, predominantly 3'-phosphotyrosyl bonds resulting from the trapping of topoisomerase I (Top1) cleavage complexes...
  7. Takashima H, Boerkoel C, John J, Saifi G, Salih M, Armstrong D, et al. Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy. Nat Genet. 2002;32:267-72 pubmed
    Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs covalently bound topoisomerase I-DNA complexes and is essential for preventing the formation of double-strand breaks that result when stalled topoisomerase I complexes interfere with DNA ..
  8. Chiang S, Carroll J, El Khamisy S. TDP1 serine 81 promotes interaction with DNA ligase IIIalpha and facilitates cell survival following DNA damage. Cell Cycle. 2010;9:588-595 pubmed
    Tyrosyl DNA phosphodiesterase (TDP1) is a DNA 3'-end processing enzyme that preferentially hydrolyses the bond between the 3'-end of DNA and stalled DNA topoisomerase 1...
  9. Hudson J, Chiang S, Wells O, Rookyard C, El Khamisy S. SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair. Nat Commun. 2012;3:733 pubmed publisher
    ..This is typified by defects in tyrosyl DNA phosphodiesterase 1 (TDP1), which removes stalled topoisomerase 1 peptides from DNA termini...

More Information

Publications102 found, 100 shown here

  1. Pouliot J, Yao K, Robertson C, Nash H. Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes. Science. 1999;286:552-5 pubmed
    ..The presence of this gene in humans may have implications for the effectiveness of topoisomerase I poisons, such as the camptothecins, in chemotherapy. ..
  2. Interthal H, Chen H, Kehl Fie T, Zotzmann J, Leppard J, Champoux J. SCAN1 mutant Tdp1 accumulates the enzyme--DNA intermediate and causes camptothecin hypersensitivity. EMBO J. 2005;24:2224-33 pubmed
    Tyrosyl-DNA phosphodiesterase (Tdp1) catalyzes the hydrolysis of the tyrosyl-3' phosphate linkage found in topoisomerase I-DNA covalent complexes...
  3. Gajewski S, Comeaux E, Jafari N, Bharatham N, Bashford D, White S, et al. Analysis of the active-site mechanism of tyrosyl-DNA phosphodiesterase I: a member of the phospholipase D superfamily. J Mol Biol. 2012;415:741-58 pubmed publisher
    Tyrosyl-DNA phosphodiesterase I (Tdp1) is a member of the phospholipase D superfamily that hydrolyzes 3'-phospho-DNA adducts via two conserved catalytic histidines-one acting as the lead nucleophile and the second acting as a general acid/..
  4. Davies D, Interthal H, Champoux J, Hol W. Crystal structure of a transition state mimic for Tdp1 assembled from vanadate, DNA, and a topoisomerase I-derived peptide. Chem Biol. 2003;10:139-47 pubmed
    Tyrosyl-DNA phosphodiesterase (Tdp1) is a member of the phospholipase D superfamily and acts as a DNA repair enzyme that removes stalled topoisomerase I- DNA complexes by hydrolyzing the bond between a tyrosine side chain and a DNA 3' ..
  5. Hubert L, Lin Y, Dion V, Wilson J. Topoisomerase 1 and single-strand break repair modulate transcription-induced CAG repeat contraction in human cells. Mol Cell Biol. 2011;31:3105-12 pubmed publisher
    ..knockdowns demonstrated the involvement of topoisomerase 1 (TOP1), tyrosyl-DNA phosphodiesterase 1 (TDP1), and single-strand break repair (SSBR) in modulating transcription-dependent CAG repeat contractions...
  6. Antony S, Marchand C, Stephen A, Thibaut L, Agama K, Fisher R, et al. Novel high-throughput electrochemiluminescent assay for identification of human tyrosyl-DNA phosphodiesterase (Tdp1) inhibitors and characterization of furamidine (NSC 305831) as an inhibitor of Tdp1. Nucleic Acids Res. 2007;35:4474-84 pubmed
    ..hydrolyzing the terminal phosphodiester bond at the 3'-ends of DNA breaks, tyrosyl-DNA phosphodiesterase (Tdp1) repairs topoisomerase-DNA covalent complexes and processes the DNA ends for DNA repair...
  7. Davies D, Interthal H, Champoux J, Hol W. Insights into substrate binding and catalytic mechanism of human tyrosyl-DNA phosphodiesterase (Tdp1) from vanadate and tungstate-inhibited structures. J Mol Biol. 2002;324:917-32 pubmed
    Tyrosyl-DNA phosphodiesterase (Tdp1) is a DNA repair enzyme that catalyzes the hydrolysis of a phosphodiester bond between a tyrosine residue and a DNA 3'-phosphate...
  8. Raymond A, Rideout M, Staker B, Hjerrild K, Burgin A. Analysis of human tyrosyl-DNA phosphodiesterase I catalytic residues. J Mol Biol. 2004;338:895-906 pubmed
    Tyrosyl-DNA phosphodiesterase I (Tdp1) is involved in the repair of DNA lesions created by topoisomerase I in vivo...
  9. Das B, Antony S, Gupta S, Dexheimer T, Redon C, Garfield S, et al. Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA-PK. EMBO J. 2009;28:3667-80 pubmed publisher
    Human tyrosyl-DNA phosphodiesterase (TDP1) hydrolyzes the phosphodiester bond at a DNA 3' end linked to a tyrosyl moiety...
  10. Barthelmes H, Habermeyer M, Christensen M, Mielke C, Interthal H, Pouliot J, et al. TDP1 overexpression in human cells counteracts DNA damage mediated by topoisomerases I and II. J Biol Chem. 2004;279:55618-25 pubmed
    b>Tyrosyl DNA phosphodiesterase 1 (TDP1) is a repair enzyme that removes adducts, e.g. of topoisomerase I from the 3'-phosphate of DNA breaks...
  11. El Khamisy S, Saifi G, Weinfeld M, Johansson F, Helleday T, Lupski J, et al. Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1. Nature. 2005;434:108-13 pubmed
    ..neuropathy-1 (SCAN1) is a neurodegenerative disease that results from mutation of tyrosyl phosphodiesterase 1 (TDP1)...
  12. Zhou T, Lee J, Tatavarthi H, Lupski J, Valerie K, Povirk L. Deficiency in 3'-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1). Nucleic Acids Res. 2005;33:289-97 pubmed
    Tyrosyl-DNA phosphodiesterase (TDP1) is a DNA repair enzyme that removes peptide fragments linked through tyrosine to the 3' end of DNA, and can also remove 3'-phosphoglycolates (PGs) formed by free radical-mediated DNA cleavage...
  13. Miao Z, Agama K, Sordet O, Povirk L, Kohn K, Pommier Y. Hereditary ataxia SCAN1 cells are defective for the repair of transcription-dependent topoisomerase I cleavage complexes. DNA Repair (Amst). 2006;5:1489-94 pubmed
    ..neuropathy (SCAN1) is caused by an inactivating mutation (H493R) in the enzyme tyrosyl-DNA phosphodiesterase (Tdp1), which removes blocked 3'-termini at DNA strand breaks...
  14. He X, van Waardenburg R, Babaoglu K, Price A, Nitiss K, Nitiss J, et al. Mutation of a conserved active site residue converts tyrosyl-DNA phosphodiesterase I into a DNA topoisomerase I-dependent poison. J Mol Biol. 2007;372:1070-81 pubmed
    Tyrosyl-DNA phosphodiesterase 1 (Tdp1) catalyzes the resolution of 3' and 5' phospho-DNA adducts. A defective mutant, associated with the recessive neurodegenerative disease SCAN1, accumulates Tdp1-DNA complexes in vitro...
  15. Interthal H, Pouliot J, Champoux J. The tyrosyl-DNA phosphodiesterase Tdp1 is a member of the phospholipase D superfamily. Proc Natl Acad Sci U S A. 2001;98:12009-14 pubmed
    ..Based on sequence comparisons, we show here that the tyrosyl-DNA phosphodiesterase (Tdp1) that has been implicated in the repair of topoisomerase I covalent complexes with DNA contains two unusual HKD ..
  16. Hirano R, Interthal H, Huang C, Nakamura T, Deguchi K, Choi K, et al. Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation?. EMBO J. 2007;26:4732-43 pubmed
    Tyrosyl-DNA phosphodiesterase 1 (Tdp1) cleaves the phosphodiester bond between a covalently stalled topoisomerase I (Topo I) and the 3' end of DNA...
  17. Interthal H, Chen H, Champoux J. Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages. J Biol Chem. 2005;280:36518-28 pubmed
    Human tyrosyl-DNA phosphodiesterase (Tdp1) hydrolyzes the phosphodiester bond between a DNA 3' end and a tyrosyl moiety...
  18. Zhou T, Akopiants K, Mohapatra S, Lin P, Valerie K, Ramsden D, et al. Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks. DNA Repair (Amst). 2009;8:901-11 pubmed publisher
    Although tyrosyl-DNA phosphodiesterase (TDP1) is capable of removing blocked 3' termini from DNA double-strand break ends, it is uncertain whether this activity plays a role in double-strand break repair...
  19. Das B, Dexheimer T, Maddali K, Pommier Y. Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria. Proc Natl Acad Sci U S A. 2010;107:19790-5 pubmed publisher
    Human tyrosyl-DNA phosphodiesterase (TDP1) hydrolyzes the phosphodiester bond at a DNA 3'-end linked to a tyrosyl moiety and has been implicated in the repair of topoisomerase I (Top1)-DNA covalent complexes...
  20. Murai J, Huang S, Das B, Dexheimer T, Takeda S, Pommier Y. Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs DNA damage induced by topoisomerases I and II and base alkylation in vertebrate cells. J Biol Chem. 2012;287:12848-57 pubmed publisher
    Tyrosyl-DNA phosphodiesterase 1 (Tdp1) repairs topoisomerase I cleavage complexes (Top1cc) by hydrolyzing their 3'-phosphotyrosyl DNA bonds and repairs bleomycin-induced DNA damage by hydrolyzing 3'-phosphoglycolates...
  21. Guo D, Dexheimer T, Pommier Y, Nash H. Neuroprotection and repair of 3'-blocking DNA ends by glaikit (gkt) encoding Drosophila tyrosyl-DNA phosphodiesterase 1 (TDP1). Proc Natl Acad Sci U S A. 2014;111:15816-20 pubmed publisher
    Tyrosyl-DNA phosphodiesterase (TDP1) is a phylogenetically conserved enzyme critical for the removal of blocking lesions at the 3' ends of DNA or RNA...
  22. Enderle J, Dorn A, Beying N, Trapp O, Puchta H. The protease WSS1A, the endonuclease MUS81 and the phosphodiesterase TDP1 are involved in independent pathways of DNA-protein crosslink repair in plants. Plant Cell. 2019;: pubmed publisher
    ..Interestingly, the CRISPR/Cas9 mutants of the tyrosyl-DNA phosphodiesterase 1 (TDP1) are insensitive to CPT, and only the wss1A tdp1 double mutant reveals a higher sensitivity than the wss1A single ..
  23. Das B, Huang S, Murai J, Rehman I, Ame J, Sengupta S, et al. PARP1-TDP1 coupling for the repair of topoisomerase I-induced DNA damage. Nucleic Acids Res. 2014;42:4435-49 pubmed publisher
    ..Endogenous and carcinogenic DNA lesions can also trap Top1cc. Tyrosyl-DNA phosphodiesterase 1 (TDP1), a key repair enzyme for trapped Top1cc, hydrolyzes the phosphodiester bond between the DNA 3'-end and the Top1 ..
  24. Murai J, Marchand C, Shahane S, Sun H, Huang R, Zhang Y, et al. Identification of novel PARP inhibitors using a cell-based TDP1 inhibitory assay in a quantitative high-throughput screening platform. DNA Repair (Amst). 2014;21:177-82 pubmed publisher
    ..These lesions are repaired by parallel repair pathways including the tyrosyl-DNA phosphodiesterase 1 (TDP1)-related pathway and homologous recombination...
  25. Adhikari S, Karmahapatra S, Elias H, Dhopeshwarkar P, Williams R, Byers S, et al. Development of a novel assay for human tyrosyl DNA phosphodiesterase 2. Anal Biochem. 2011;416:112-6 pubmed publisher
    ..b>Tyrosyl DNA phosphodiesterase 1 (TDP1) and human AP-endonuclease 1 (APE1) could not hydrolyze T5PNP...
  26. Sykora P, Wilson D, Bohr V. Repair of persistent strand breaks in the mitochondrial genome. Mech Ageing Dev. 2012;133:169-75 pubmed publisher
    ..BER, including Cockayne syndrome proteins A and B (CSA and CSB), aprataxin (APTX), tryosyl-DNA phosphodiesterase 1 (TDP1), flap endonuclease 1 (FEN-1) and exonuclease G (EXOG)...
  27. Huang S, Pommier Y, Marchand C. Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) inhibitors. Expert Opin Ther Pat. 2011;21:1285-92 pubmed publisher
    ..One line of inquiry focuses on inhibitors of tyrosyl-DNA phosphodiesterase 1 (Tdp1), a repair enzyme for Top1cc...
  28. Maede Y, Shimizu H, Fukushima T, Kogame T, Nakamura T, Miki T, et al. Differential and common DNA repair pathways for topoisomerase I- and II-targeted drugs in a genetic DT40 repair cell screen panel. Mol Cancer Ther. 2014;13:214-20 pubmed publisher
    ..Most distinct repair pathways between Top1 and Top2 inhibitors include NHEJ, TDP1, TDP2, PARP1, and Fanconi Anemia genes, whereas homologous recombination seems relevant especially for Top1 and, to ..
  29. Königer C, Wingert I, Marsmann M, Rösler C, Beck J, Nassal M. Involvement of the host DNA-repair enzyme TDP2 in formation of the covalently closed circular DNA persistence reservoir of hepatitis B viruses. Proc Natl Acad Sci U S A. 2014;111:E4244-53 pubmed publisher
    ..Here we demonstrate that human and chicken TDP2, but only the yeast ortholog of TDP1, can specifically cleave the Tyr-DNA bond in virus-adapted model substrates and release P protein from authentic ..
  30. Liang J, Ning X, Sun J, Song J, Lu J, Cai H, et al. Toxicity evaluation of textile dyeing effluent and its possible relationship with chemical oxygen demand. Ecotoxicol Environ Saf. 2018;166:56-62 pubmed publisher
    ..for removing macromolecular organic substances, and membrane filtration and sedimentation basin employed at TDP1 and TDP2, respectively, helped to remove toxic substances. Toxicity to V. fischeri or D...
  31. Alagoz M, Gilbert D, El Khamisy S, Chalmers A. DNA repair and resistance to topoisomerase I inhibitors: mechanisms, biomarkers and therapeutic targets. Curr Med Chem. 2012;19:3874-85 pubmed
    ..This review summarises the current status of these research endeavours, focusing on the key roles of tyrosyl DNA phosphodiesterase 1 (Tdp1) and poly(ADP-ribose) polymerase (PARP), and examines the pre-clinical and clinical data that ..
  32. Liao C, Beveridge R, Hudson J, Parker J, Chiang S, Ray S, et al. UCHL3 Regulates Topoisomerase-Induced Chromosomal Break Repair by Controlling TDP1 Proteostasis. Cell Rep. 2018;23:3352-3365 pubmed publisher
    ..This is typified by tyrosyl DNA phosphodiesterase 1 (TDP1), which repairs topoisomerase-mediated chromosomal breaks...
  33. Pommier Y. Drugging topoisomerases: lessons and challenges. ACS Chem Biol. 2013;8:82-95 pubmed publisher
    ..activity and patient selection, prospects of rational combinations with DNA repair inhibitors targeting tyrosyl-DNA-phosphodiesterases 1 and 2 (TDP1 and TDP2) and PARP, and the unmet need to develop inhibitors for type IA enzymes.
  34. Nguyen T, Abdelmalak M, Marchand C, Agama K, Pommier Y, Cushman M. Synthesis and biological evaluation of nitrated 7-, 8-, 9-, and 10-hydroxyindenoisoquinolines as potential dual topoisomerase I (Top1)-tyrosyl-DNA phosphodiesterase I (TDP1) inhibitors. J Med Chem. 2015;58:3188-208 pubmed publisher
    The structure-activity relationships and hit-to-lead optimization of dual Top1-TDP1 inhibitors in the indenoisoquinoline drug class were investigated...
  35. Zhang Y, Wang Z, Li D, Zang W, Zhu H, Wu P, et al. A polysaccharide from Antrodia cinnamomea mycelia exerts antitumor activity through blocking of TOP1/TDP1-mediated DNA repair pathway. Int J Biol Macromol. 2018;120:1551-1560 pubmed publisher
    ..arrest (cells remained in G2/M phase) through blocking of topoisomerase I/tyrosyl-DNA phosphodiesterase I (TOP1/TDP1)-mediated DNA repair pathway...
  36. Li Zhulanov N, Zakharenko A, Chepanova A, Patel J, Zafar A, Volcho K, et al. A Novel Class of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Contains the Octahydro-2H-chromen-4-ol Scaffold. Molecules. 2018;23: pubmed publisher
    Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that mends topoisomerase 1-mediated DNA damage...
  37. Nakatani R, Nakamori M, Fujimura H, Mochizuki H, Takahashi M. Large expansion of CTG•CAG repeats is exacerbated by MutSβ in human cells. Sci Rep. 2015;5:11020 pubmed publisher
    ..Knockdown of topoisomerase 1 (TOP1) and TDP1, which are involved in single-strand break repair, enhanced large repeat contractions...
  38. Fam H, Choi K, Fougner L, Lim C, Boerkoel C. Reactive oxygen species stress increases accumulation of tyrosyl-DNA phsosphodiesterase 1 within mitochondria. Sci Rep. 2018;8:4304 pubmed publisher
    Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a nuclear and mitochondrial protein that in nuclei and in vitro repairs blocked 3' DNA termini such as 3' phosphotyrosine conjugates resulting from stalling of topoisomerase I-DNA intermediates...
  39. Elsayed W, El Shafie L, Hassan M, Farag M, El Khamisy S. Isoeugenol is a selective potentiator of camptothecin cytotoxicity in vertebrate cells lacking TDP1. Sci Rep. 2016;6:26626 pubmed publisher
    ..utilising a selection of natural compounds in the presence or absence of tyrosyl DNA phosphodiesterase I (TDP1); a key TOP1-mediated protein-linked DNA break (PDB) repair enzyme...
  40. Kiselev E, Dexheimer T, Marchand C, Huang S, Pommier Y. Probing the evolutionary conserved residues Y204, F259, S400 and W590 that shape the catalytic groove of human TDP1 for 3'- and 5'-phosphodiester-DNA bond cleavage. DNA Repair (Amst). 2018;66-67:64-71 pubmed publisher
    Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an ubiquitous DNA repair enzyme present in yeast, plants and animals. It removes a broad range of blocking lesions at the ends of DNA breaks...
  41. Sparks J, Burgers P. Error-free and mutagenic processing of topoisomerase 1-provoked damage at genomic ribonucleotides. EMBO J. 2015;34:1259-69 pubmed publisher
    ..show that these covalent complexes can be processed by proteolysis, followed by removal of the phospho-peptide by Tdp1 and the 3'-phosphate by Tpp1 to mediate error-free repair...
  42. Dean R, Fam H, An J, Choi K, Shimizu Y, Jones S, et al. Identification of a putative Tdp1 inhibitor (CD00509) by in vitro and cell-based assays. J Biomol Screen. 2014;19:1372-82 pubmed publisher
    ..Given that tyrosyl-DNA phosphodiesterase 1 (Tdp1) repairs stalled topoisomerase-I DNA complexes, we hypothesized that inhibition of Tdp1 has synthetic lethal ..
  43. Blasiak J. DNA-Damaging Anticancer Drugs - A Perspective for DNA Repair- Oriented Therapy. Curr Med Chem. 2017;24:1488-1503 pubmed publisher
    ..by several pathways, but 3'PGs must be processed to the 3'-OH ends, usually by tyrosyl-DNA phosphodiesterase 1 (Tdp1). Therefore, targeting Tdp1 can improve anticancer therapy with BLM...
  44. Cristini A, Park J, Capranico G, Legube G, Favre G, Sordet O. DNA-PK triggers histone ubiquitination and signaling in response to DNA double-strand breaks produced during the repair of transcription-blocking topoisomerase I lesions. Nucleic Acids Res. 2016;44:1161-78 pubmed publisher
    ..lesions whose repair depends primarily on Top1 proteolysis and excision by tyrosyl-DNA phosphodiesterase-1 (TDP1). We previously reported that stabilized Top1cc produce transcription-dependent DSBs that activate ATM in neurons...
  45. Alagoz M, Chiang S, Sharma A, El Khamisy S. ATM deficiency results in accumulation of DNA-topoisomerase I covalent intermediates in neural cells. PLoS ONE. 2013;8:e58239 pubmed publisher
    ..This is typified by defects in tyrosyl DNA phosphodiesterase 1 (TDP1) and human hereditary ataxia...
  46. Duffy S, Fam H, Wang Y, Styles E, Kim J, Ang J, et al. Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer. Proc Natl Acad Sci U S A. 2016;113:9967-76 pubmed publisher
    ..We show that two genes, TDP1, a tyrosyl-DNA-phosphdiesterase, and TAF12, an RNA polymerase II TATA-box binding factor, cause CIN when ..
  47. Meisenberg C, Ashour M, El Shafie L, Liao C, Hodgson A, Pilborough A, et al. Epigenetic changes in histone acetylation underpin resistance to the topoisomerase I inhibitor irinotecan. Nucleic Acids Res. 2017;45:1159-1176 pubmed publisher
    ..to downregulation of the main cellular target of irinotecan TOP1 nor upregulation of the key TOP1 PDB repair factor TDP1. Instead, the faster repair of PDBs underlies resistance, which is associated with perturbed histone H4K16 ..
  48. Toots M, Männik A, Mumm K, Tämm K, Tamm T, Ustav E, et al. Identification of several high-risk HPV inhibitors and drug targets with a novel high-throughput screening assay. PLoS Pathog. 2017;13:e1006168 pubmed publisher
    ..At least five of the inhibitors block the function of Tdp1 and PARP1, which have been identified as essential cellular proteins for HPV replication and promising candidates ..
  49. Wang P, Elsayed M, Plescia C, Ravji A, Redon C, Kiselev E, et al. Synthesis and Biological Evaluation of the First Triple Inhibitors of Human Topoisomerase 1, Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), and Tyrosyl-DNA Phosphodiesterase 2 (Tdp2). J Med Chem. 2017;60:3275-3288 pubmed publisher
    b>Tdp1 and Tdp2 are two tyrosyl-DNA phosphodiesterases that can repair damaged DNA resulting from topoisomerase inhibitors and a variety of other DNA-damaging agents...
  50. Moor N, Vasil eva I, Anarbaev R, Antson A, Lavrik O. Quantitative characterization of protein-protein complexes involved in base excision DNA repair. Nucleic Acids Res. 2015;43:6009-22 pubmed publisher
    ..polymerase 1 (PARP1), X-ray repair cross-complementing protein 1 (XRCC1) and tyrosyl-DNA phosphodiesterase 1 (TDP1), using fluorescence- and light scattering-based techniques...
  51. Menon V, Povirk L. End-processing nucleases and phosphodiesterases: An elite supporting cast for the non-homologous end joining pathway of DNA double-strand break repair. DNA Repair (Amst). 2016;43:57-68 pubmed publisher
    ..Several additional DNA end-specific phosphodiesterases, including TDP1, TDP2 and aprataxin are available to resolve various non-nucleotide moieties at DSB ends...
  52. Hoskins J, Rosner G, Ratain M, McLeod H, Innocenti F. Pharmacodynamic genes do not influence risk of neutropenia in cancer patients treated with moderately high-dose irinotecan. Pharmacogenomics. 2009;10:1139-46 pubmed publisher
    A recent study found that variation in camptothecin pharmacodynamic genes (TOP1, PARP1, TDP1 and XRCC1) correlated with efficacy and risk of neutropenia in irinotecan-treated cancer patients (median dose: 180 mg/m2), which suggests that ..
  53. Balakirev M, Mullally J, Favier A, Assard N, Sulpice E, Lindsey D, et al. Wss1 metalloprotease partners with Cdc48/Doa1 in processing genotoxic SUMO conjugates. elife. 2015;4: pubmed publisher
    ..In cells lacking Tdp1, clearance of topoisomerase covalent complexes becomes SUMO and Wss1-dependent...
  54. Flett F, Ruksenaite E, Armstrong L, Bharati S, Carloni R, Morris E, et al. Structural basis for DNA 3'-end processing by human tyrosyl-DNA phosphodiesterase 1. Nat Commun. 2018;9:24 pubmed publisher
    Tyrosyl-DNA phosphodiesterase (Tdp1) is a DNA 3'-end processing enzyme that repairs topoisomerase 1B-induced DNA damage...
  55. Comeaux E, Cuya S, Kojima K, Jafari N, Wanzeck K, Mobley J, et al. Tyrosyl-DNA phosphodiesterase I catalytic mutants reveal an alternative nucleophile that can catalyze substrate cleavage. J Biol Chem. 2015;290:6203-14 pubmed publisher
    Tyrosyl-DNA phosphodiesterase I (Tdp1) catalyzes the repair of 3'-DNA adducts, such as the 3'-phosphotyrosyl linkage of DNA topoisomerase I to DNA...
  56. Aresta Branco F, Pimenta S, Figueiredo L. A transcription-independent epigenetic mechanism is associated with antigenic switching in Trypanosoma brucei. Nucleic Acids Res. 2016;44:3131-46 pubmed publisher
    ..This conformation is independent of the cell-cycle stage, but dependent upon TDP1, a high mobility group box protein...
  57. Prasad R, Dyrkheeva N, Williams J, Wilson S. Mammalian Base Excision Repair: Functional Partnership between PARP-1 and APE1 in AP-Site Repair. PLoS ONE. 2015;10:e0124269 pubmed publisher
    ..five tightly associated and abundant BER factors in the complex: PARP-1, XRCC1, DNA ligase III, PNKP, and Tdp1. AP endonuclease 1 (APE1), however, was not present...
  58. Beck D, Lv W, Abdelmalak M, Plescia C, Agama K, Marchand C, et al. Synthesis and biological evaluation of new fluorinated and chlorinated indenoisoquinoline topoisomerase I poisons. Bioorg Med Chem. 2016;24:1469-79 pubmed publisher
    ..indenoisoquinoline Top1 inhibitors was found to also impart inhibitory activity against tyrosyl DNA phosphodiesterases 1 and 2 (TDP1 and TDP2), which are enzymes that participate in the repair of DNA damage induced by Top1 poisons.
  59. Elsayed M, Su Y, Wang P, Sethi T, Agama K, Ravji A, et al. Design and Synthesis of Chlorinated and Fluorinated 7-Azaindenoisoquinolines as Potent Cytotoxic Anticancer Agents That Inhibit Topoisomerase I. J Med Chem. 2017;60:5364-5376 pubmed publisher
    ..of the new Top1 inhibitors also possess moderate inhibitory activities against tyrosyl-DNA phosphodiesterase 1 (TDP1) and tyrosyl-DNA phosphodiesterase 2 (TDP2), two enzymes that are involved in DNA damage repair resulting from Top1 ..
  60. Salomatina O, Popadyuk I, Zakharenko A, Zakharova O, Fadeev D, Komarova N, et al. Novel Semisynthetic Derivatives of Bile Acids as Effective Tyrosyl-DNA Phosphodiesterase 1 Inhibitors. Molecules. 2018;23: pubmed publisher
    ..Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is one of the DNA repair system enzymes involved in the removal of DNA damages caused by topoisomerase I ..
  61. Lebedeva N, Rechkunova N, Ishchenko A, Saparbaev M, Lavrik O. The mechanism of human tyrosyl-DNA phosphodiesterase 1 in the cleavage of AP site and its synthetic analogs. DNA Repair (Amst). 2013;12:1037-42 pubmed publisher
    ..of the apurinic/apyrimidinic (AP) site and its synthetic analogs by using tyrosyl-DNA phosphodiesterase 1 (Tdp1) was analyzed...
  62. Wu B, Lin W, Chou I, Liu H, Lee C, Tsai Y, et al. Association of tyrosyl-DNA phosphodiesterase 1 polymorphism with Tourette syndrome in Taiwanese patients. J Clin Lab Anal. 2013;27:323-7 pubmed publisher
    ..Previous studies also showed that tyrosyl-DNA phosphodiesterase 1 (TDP1) interacts with XRCC1 to repair damaged DNA. However, the relationship between TS and SNPs of TDP1 gene is unknown...
  63. Alagoz M, Wells O, El Khamisy S. TDP1 deficiency sensitizes human cells to base damage via distinct topoisomerase I and PARP mechanisms with potential applications for cancer therapy. Nucleic Acids Res. 2014;42:3089-103 pubmed publisher
    ..Here, we report that depletion of Tyrosyl DNA phosphodiesterase 1 (TDP1) sensitizes human cells to alkylation damage and the additional depletion of apurinic/..
  64. Davies D, Interthal H, Champoux J, Hol W. Explorations of peptide and oligonucleotide binding sites of tyrosyl-DNA phosphodiesterase using vanadate complexes. J Med Chem. 2004;47:829-37 pubmed
    Tyrosyl-DNA phosphodiesterase (Tdp1) catalyzes the hydrolysis of a phosphodiester bond between a tyrosine residue and a DNA 3' phosphate and functions as a DNA repair enzyme that cleaves stalled topoisomerase I-DNA complexes...
  65. Yang M, Kirley T. Site-directed mutagenesis of human soluble calcium-activated nucleotidase 1 (hSCAN-1): identification of residues essential for enzyme activity and the Ca(2+)-induced conformational change. Biochemistry. 2004;43:9185-94 pubmed
  66. Pommier Y, Huang S, Gao R, Das B, Murai J, Marchand C. Tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2). DNA Repair (Amst). 2014;19:114-29 pubmed publisher
    b>TDP1 and TDP2 were discovered and named based on the fact they process 3'- and 5'-DNA ends by excising irreversible protein tyrosyl-DNA complexes involving topoisomerases I and II, respectively...
  67. Lohavanichbutr P, Sakoda L, Amos C, Arnold S, Christiani D, Davies M, et al. Common TDP1 Polymorphisms in Relation to Survival among Small Cell Lung Cancer Patients: A Multicenter Study from the International Lung Cancer Consortium. Clin Cancer Res. 2017;23:7550-7557 pubmed publisher
    ..Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome...
  68. DeYonker N, Webster C. A Theoretical Study of Phosphoryl Transfers of Tyrosyl-DNA Phosphodiesterase I (Tdp1) and the Possibility of a "Dead-End" Phosphohistidine Intermediate. Biochemistry. 2015;54:4236-47 pubmed publisher
    Tyrosyl-DNA phosphodiesterase I (Tdp1) is a DNA repair enzyme conserved across eukaryotes that catalyzes the hydrolysis of the phosphodiester bond between the tyrosine residue of topoisomerase I and the 3'-phosphate of DNA...
  69. Sharma P, Mullen J, Li M, Zaratiegui M, Bunting S, Brill S. A Lysine Desert Protects a Novel Domain in the Slx5-Slx8 SUMO Targeted Ub Ligase To Maintain Sumoylation Levels in Saccharomyces cerevisiae. Genetics. 2017;206:1807-1821 pubmed publisher
    ..Yeast cells lacking the repair factors TDP1 and WSS1 are synthetically lethal due to their redundant roles in removing Top1-DNA covalent complexes (..
  70. Sabatini M, Pagano A, Araújo S, Balestrazzi A, Macovei A. The Tyrosyl-DNA Phosphodiesterase 1? (Tdp1?) Gene Discloses an Early Response to Abiotic Stresses. Genes (Basel). 2017;8: pubmed publisher
    Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is involved in DNA repair pathways as it mends the topoisomerase I-DNA covalent complexes...
  71. Li J, Summerlin M, Nitiss K, Nitiss J, HANAKAHI L. TDP1 is required for efficient non-homologous end joining in human cells. DNA Repair (Amst). 2017;60:40-49 pubmed publisher
    Tyrosyl-DNA phosphodiesterase 1 (TDP1) can remove a wide variety of 3' and 5' terminal DNA adducts...
  72. Horton J, Stefanick D, Zhao M, Janoshazi A, Gassman N, Seddon H, et al. XRCC1-mediated repair of strand breaks independent of PNKP binding. DNA Repair (Amst). 2017;60:52-63 pubmed publisher
    ..End cleaning in mammalian cells by Tdp1 and PNKP produces the conventional 3'-OH and 5'-phosphate DNA ends suitable for completion of repair...
  73. Kawale A, Povirk L. Tyrosyl-DNA phosphodiesterases: rescuing the genome from the risks of relaxation. Nucleic Acids Res. 2017;: pubmed publisher
    Tyrosyl-DNA Phosphodiesterases 1 (TDP1) and 2 (TDP2) are eukaryotic enzymes that clean-up after aberrant topoisomerase activity...
  74. Gao R, Huang S, Marchand C, Pommier Y. Biochemical characterization of human tyrosyl-DNA phosphodiesterase 2 (TDP2/TTRAP): a Mg(2+)/Mn(2+)-dependent phosphodiesterase specific for the repair of topoisomerase cleavage complexes. J Biol Chem. 2012;287:30842-52 pubmed publisher
    ..The k(cat)/K(m) of TDP1 and TDP2 was determined. It was found to be 4 × 10(5) s(-1)M(-1) for TDP2 using single-stranded 5'-tyrosyl-DNA...
  75. Meisenberg C, Gilbert D, Chalmers A, Haley V, Gollins S, Ward S, et al. Clinical and cellular roles for TDP1 and TOP1 in modulating colorectal cancer response to irinotecan. Mol Cancer Ther. 2015;14:575-85 pubmed publisher
    ..The removal of TOP1 peptide from TOP1-DNA breaks is conducted by tyrosyl-DNA phosphodiesterase 1 (TDP1)...
  76. Gao R, Das B, Chatterjee R, Abaan O, Agama K, Matuo R, et al. Epigenetic and genetic inactivation of tyrosyl-DNA-phosphodiesterase 1 (TDP1) in human lung cancer cells from the NCI-60 panel. DNA Repair (Amst). 2014;13:1-9 pubmed publisher
    Tyrosyl-DNA-phosphodiesterase 1 (TDP1) repairs 3'-blocking DNA lesions by catalytically hydrolyzing the tyrosyl-DNA-phosphodiester bond of trapped topoisomerase I (Top1) cleavage complexes (Top1cc)...
  77. Lebedeva N, Anarbaev R, Sukhanova M, Vasil eva I, Rechkunova N, Lavrik O. Poly(ADP-ribose)polymerase 1 stimulates the AP-site cleavage activity of tyrosyl-DNA phosphodiesterase 1. Biosci Rep. 2015;35: pubmed publisher
    ..1 (PARP1) on the apurinic/apyrimidinic (AP)-site cleavage activity of tyrosyl-DNA phosphodiesterase 1 (TDP1) and interaction of PARP1 and TDP1 were studied...
  78. Chiang S, Liversidge K, El Khamisy S. Studying TDP1 Function in DNA Repair. Methods Mol Biol. 2018;1703:173-181 pubmed publisher
    ..In vertebrates, Tyrosyl-DNA phosphodiesterase 1 (TDP1) plays a major role in removal of topoisomerase 1-associated PDBs in the nucleus and mitochondria by hydrolyzing ..
  79. Adhikari S, Karmahapatra S, Karve T, Bandyopadhyay S, Woodrick J, Manthena P, et al. Characterization of magnesium requirement of human 5'-tyrosyl DNA phosphodiesterase mediated reaction. BMC Res Notes. 2012;5:134 pubmed publisher
    ..3'-phosphotyrosyl bonds can be repaired by tyrosyl DNA phosphodiesterase-1 (TDP1), an enzyme known for years, but a complementary human enzyme 5'-tyrosyl DNA phosphodiesterase (hTDP2) that cleaves ..
  80. Al Abo M, Sasanuma H, Liu X, Rajapakse V, Huang S, Kiselev E, et al. TDP1 is Critical for the Repair of DNA Breaks Induced by Sapacitabine, a Nucleoside also Targeting ATM- and BRCA-Deficient Tumors. Mol Cancer Ther. 2017;16:2543-2551 pubmed publisher
    ..Because tyrosyl-DNA phosphodiesterase 1 (TDP1) selectively hydrolyzes nonphosphorylated 3'-blocking ends, we tested its role in the repair of CNDAC-induced DNA ..
  81. Jun J, Kumar V, Dexheimer T, Wedlich I, Nicklaus M, Pommier Y, et al. Synthesis, anti-cancer screening and tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibition activity of novel piperidinyl sulfamides. Eur J Pharm Sci. 2018;111:337-348 pubmed publisher
    ..1?M for SW-620 cells. These newly synthesized sulfamides were also screening for their Tdp1 inhibition activity. Compound 18 (NSC 750706) showed significant inhibition of Tdp1 with IC50=23.7?M...
  82. Liu C, Zhou S, Begum S, Sidransky D, Westra W, Brock M, et al. Increased expression and activity of repair genes TDP1 and XPF in non-small cell lung cancer. Lung Cancer. 2007;55:303-11 pubmed
    ..Top1) inhibitor, is frequently encountered in non-small cell lung cancer (NSCLC) and CPT resistance is linked with TDP1, an enzyme capable of cleaving the covalent linkage between stabilized Top1 with DNA...
  83. Heo J, Li J, Summerlin M, Hays A, Katyal S, McKinnon P, et al. TDP1 promotes assembly of non-homologous end joining protein complexes on DNA. DNA Repair (Amst). 2015;30:28-37 pubmed publisher
    ..In yeast, mutations of tyrosyl-DNA phosphodiesterase (TDP1) reduced NHEJ fidelity...
  84. Jakobsen A, Lauridsen K, Samuel E, Proszek J, Knudsen B, Hager H, et al. Correlation between topoisomerase I and tyrosyl-DNA phosphodiesterase 1 activities in non-small cell lung cancer tissue. Exp Mol Pathol. 2015;99:56-64 pubmed publisher
    ..I (TOP1) regulates DNA topology during replication and transcription whereas tyrosyl-DNA phosphodiesterase 1 (TDP1) is involved in the repair of several types of DNA damages, including damages from defective TOP1 catalysis...
  85. Jiang B, Glover J, Weinfeld M. Neurological disorders associated with DNA strand-break processing enzymes. Mech Ageing Dev. 2017;161:130-140 pubmed publisher
    ..The three proteins, tyrosyl DNA-phosphodiesterase 1 (TDP1), aprataxin (APTX) and polynucleotide kinase/phosphatase (PNKP) each act on a discrete set of modified strand-break ..
  86. Fam H, Walton C, Mitra S, Chowdhury M, Osborne N, Choi K, et al. TDP1 and PARP1 deficiency are cytotoxic to rhabdomyosarcoma cells. Mol Cancer Res. 2013;11:1179-92 pubmed publisher
    ..failure of irinotecan may be the result of overexpression of the DNA repair enzyme tyrosyl-DNA phosphodiesterase (TDP1), which processes topoisomerase I-DNA complexes resulting from topoisomerase I inhibitor treatment...
  87. Takiuchi Y, Kobayashi M, Tada K, Iwai F, Sakurada M, Hirabayashi S, et al. HTLV-1 bZIP factor suppresses TDP1 expression through inhibition of NRF-1 in adult T-cell leukemia. Sci Rep. 2017;7:12849 pubmed publisher
    ..This effect was attributed to the reduced expression of tyrosyl-DNA-phosphodiesterase 1 (TDP1), a DNA repair enzyme, in ATL cells...
  88. Huang H, Liu J, Baglo Y, Rizvi I, Anbil S, Pigula M, et al. Mechanism-informed Repurposing of Minocycline Overcomes Resistance to Topoisomerase Inhibition for Peritoneal Carcinomatosis. Mol Cancer Ther. 2018;17:508-520 pubmed publisher
    ..minocycline, by its ability to minimize DNA repair via reduced expression of tyrosyl-DNA phosphodiesterase-1 (Tdp1), removes a key process attenuating the efficacy of irinotecan, a frequently used chemotherapeutic against ..
  89. El Khamisy S, Caldecott K. TDP1-dependent DNA single-strand break repair and neurodegeneration. Mutagenesis. 2006;21:219-24 pubmed
    ..Although it is a rare neurodegenerative disease, understanding the molecular basis of SCAN1 will lead to better understanding of the mechanisms that underpin not only neurodegeneration but also cancer. ..
  90. Cuya S, Comeaux E, Wanzeck K, Yoon K, van Waardenburg R. Dysregulated human Tyrosyl-DNA phosphodiesterase I acts as cellular toxin. Oncotarget. 2016;7:86660-86674 pubmed publisher
    Tyrosyl-DNA phosphodiesterase I (TDP1) hydrolyzes the drug-stabilized 3'phospho-tyrosyl bond formed between DNA topoisomerase I (TOPO1) and DNA...
  91. Meagher M, Lightowlers R. The role of TDP1 and APTX in mitochondrial DNA repair. Biochimie. 2014;100:121-4 pubmed publisher
    ..In this short review two enzymes, tyrosyl-DNA-phosphodiesterase 1 (TDP1) and aprataxin (APTX), involved in mitochondrial single strand break repair (SSBR) are discussed...