Human Tyrosyl-DNA Phosphodiesterase 1(TDP1)ELISA Kit

DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3'exonuclease activity and can remove a single nucleoside from the 3'end of DNA and RNA molecules with 3'hydroxyl groups. Has no exonuclease activity towards DNA or RNA with a 3'phosphate.

1. The role of conserved residues Y204, F259, S400 and W590 of the catalytic groove of TDP1 protein DNA cleavage activity was analyzed. PMID: 29747024
2. We found the rs942190 GG genotype of TDP1 to be associated with relatively poor survival among small-cell lung cancer patients. Further investigation is needed to confirm the result and to determine whether this genotype may be a predictive marker for treatment efficacy of DNA topoisomerase inhibitors PMID: 28974547
3. this study identifies the importance of TDP1 as a novel determinant of response to CNDAC across various cancer types (especially non-small cell lung cancers), and demonstrates the differential involvement of BRCA2, PARP1, and TDP1 in the cellular responses to CNDAC, AraC, and CPT PMID: 28802254
4. Data indicate that the initial step of tyrosyl-DNA phosphodiesterase 1 (Tdp1) interaction with DNA includes binding of Tdp1 to the DNA ends followed by the 3'-nucleosidase reaction. PMID: 27687298
5. Data indicate a molecular basis for DNA 3'-end processing by tyrosyl-DNA phosphodiesterase (Tdp1). PMID: 29295983
6. Expression of human Tdp1HisnucAla and Tdp1HisgabAsn mutants results in stabilization of the covalent TDP1-DNA intermediate and induces cytotoxicity. PMID: 27893431
7. We show that two genes, TDP1, a tyrosyl-DNA-phosphdiesterase, and TAF12, an RNA polymerase II TATA-box binding factor, cause CIN when overexpressed in human cells. Using SDL screens in yeast, we identified a set of genes that when deleted specifically kill cells with high levels of Tdp1 PMID: 27551064
8. TDP1 participation in human non-homologous end joining (NHEJ) is mediated by interaction with XLF, and that TDP1-XLF interactions and subsequent NHEJ events are regulated by phosphorylation of TDP1-S81. PMID: 29078113
9. The data obtained suggest that PARP1 and TDP1 bind in an antiparallel orientation; the N-terminus of the former protein interacts with the C-terminal domain of the latter. PMID: 26181362
10. Tyrosyl-DNA-phosphodiesterase I (TDP1) participates in the removal and repair of stabilized-Top2alpha cleavage complexes in human cells. PMID: 26421495
11. varying expression levels of TOP1 and TDP1 polypeptides in multiple colorectal cancer cell lines and in clinical colorectal cancer samples, are reported. PMID: 25522766
12. both TOP1 and TDP1 were upregulated in the tumor tissue compared to the adjacent non-tumor tissue in non-small cell lung cancer tissue PMID: 25987486
13. Density functional theory computations are used to acquire thermodynamic and kinetic data along the catalytic pathway, including the phosphoryl transfers of Tdp1 and subsequent hydrolysis. PMID: 26121557
14. TDP1 plays a role during the early stages of mammalian NHEJ. TPD1 stimulated DNA binding by XLF. TDP1 also promoted DNA binding by Ku70/80 and stimulated DNA-PK activity. PMID: 25841101
15. These findings suggest that the flexibility of Tdp1 active site residues may impair the resolution of mutant Tdp1 covalent phosphohistidyl intermediates PMID: 25609251
16. This article summarizes and compares the biochemistry, functions, and post-translational regulation of TDP1 and TDP2, as well as the relevance of TDP1 and TDP2 as determinants of response to anticancer agents PMID: 24856239
17. Data provides insights into the possible inactivation of TDP1 in cancers and its relationship to cellular response to Top1-targeted drugs. PMID: 24355542
18. Results show Tdp1 catalyzes hydrolysis of apurinic/apyrimidinic site analog correlates with the DNA helix distortion induced by the substituent. PMID: 24183900
19. marked overexpression of TDP1 protein and mRNA in rhabdomyosarcoma tumors was observed; results suggest a compensatory role for TDP1 in rhabdomyosarcoma after topoisomerase-I based therapy PMID: 23913164
20. TDP1 deficiency sensitizes human cells to base damage, independently of apurinic/apyrimidinic endonuclease I (APE1). PMID: 24335147
21. These studies suggest that one role of cytoplasmic Tdp1 is the repair of mitochondrial DNA lesions arising from oxidative stress. PMID: 23536040
22. A polymorphism at position rs28365054 in the TDP1 gene had a significant difference (P < 0.05) in the genotype distributions between the Tourette syndrome patients and the control group PMID: 23852793
23. study identifies TDP1 as a target for modification by the small ubiquitin-like modifier SUMO and provides evidence implicating SUMOylation in facilitating TDP1 cellular function during single-strand break repair PMID: 22415824
24. Our findings reveal a broad involvement of Tdp1 in DNA repair and clarify the role of human TDP1 in the repair of Top2-induced DNA damage. PMID: 22375014
25. Analysis of the active-site mechanism of tyrosyl-DNA phosphodiesterase I. PMID: 22155078
26. topoisomerase 1, tyrosyl-DNA phosphodiesterase 1, and single-strand break repair modulate transcription-dependent CAG repeat contractions PMID: 21628532
27. Study investigates substrate specificity of Tdp1; data suggest a role for Tdp1 in a new APE-independent base excision repair pathway. PMID: 21276450
28. These findings provide evidence for TDP1 as a novel mitochondrial enzyme. PMID: 21041670
29. results suggest human Tdp1 may act using a scanning mechanism, in which Tdp1 bind non-specifically upstream of a 3'-blocking lesion and is preferentially stabilized at 3'-DNA ends corresponding to its site of action. PMID: 20097655
30. The interaction with Lig3alpha is promoted by serine 81 that is located within a putative S/TQ site in the N-terminus domain of TDP1. PMID: 20009512
31. TDP1 phosphorylation at serine residue 81 promotes cell survival and DNA repair in response to carnitine O-palmitoyltransferase-induced DNA double-strand breaks. PMID: 19851285
32. 1.69 A crystal structure of human tyrosyl-DNA phosphodiesterase PMID: 11839309
33. a role for hTdp1 in repair of free radical-mediated DNA double strand breaks bearing terminally blocked 3' overhangs. PMID: 12023295
34. loss-of-function mutations in TDP1 may cause spinocerebellar ataxia with axonal neuropathy either by interfering with DNA transcription or by inducing apoptosis in postmitotic neurons PMID: 12244316
35. We report the three-dimensional structures of human Tdp1 bound to the phosphate transition state analogs vanadate and tungstate PMID: 12470949
36. conserved sequences and amino acids important for catalytic activity and enzyme specificity were identified PMID: 15248776
37. TDP1 is required for the repair of topoisomerase I-mediated DNA damage and may have a role in the repair of DNA damage mediated by topoisomerase II PMID: 15494395
38. The role of TDP1 in 3'-phosphoglycolate processing during in vitro end joining of DNA double-strand breaks. PMID: 15647511
39. Tdp1 only acts upon double strand breaks in vivo PMID: 15811850
40. inhibitors of Tdp1 could act synergistically with camptothecin in anticancer therapy PMID: 15920477
41. Tdp1 may function to remove a variety of 3' adducts from DNA during DNA repair PMID: 16141202
42. TDP1 has a role in DNA single-strand break repair and neurodegeneration [review] PMID: 16775218
43. it is proposed that Tdp1 is involved in the repair of Top1 cleavage complexes associated with transcription damage in hereditary spinocerebellar ataxia with axonal neuropathy (SCAN1) cells PMID: 16935573
44. TDP1 is also required for the repair of single stranded breaks induced by ionizing radiation (IR), though not measurably for IR-induced DNA double-strand breaks PMID: 17600775
45. Data show that mutation of a conserved active site residue converts tyrosyl-DNA phosphodiesterase I into a DNA topoisomerase I-dependent poison. PMID: 17707402
46. This study provides a direct demonstration that Tdp1 repairs Topo I covalent lesions in vivo and suggests that spinocerebellar ataxia with axonal neuropathy (SCAN1) arises from the recessive neomorphic mutation H493R. PMID: 17948061
47. TDP1 can gain access to and can process blocked 3' termini of double-strand breaks before ends are fully sequestered by DNA-PK, as well as at a later stage after DNA-PK autophosphorylation. PMID: 19505854
48. Sequences nearly identical to FLJ11090 are highly homologous to the yeast TDP1 gene. Tdp1 protein cleaves the linkage between a phosphotyrosyl group and the 3'-end of DNA, and has been shown to be involved in the repair of TOP1-induced DNA damage. PMID: 10521354
49. Protein assay of expressed FLJ11090 shows that it encodes human tyrosyl-DNA phodphodiesterase (TDP1). PMID: 11572945

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Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy (SCAN1)

Nucleus. Cytoplasm.

Tyrosyl-DNA phosphodiesterase family

Ubiquitously expressed. Similar expression throughout the central nervous system (whole brain, amygdala, caudate nucleus, cerebellum, cerebral cortex, frontal lobe, hippocampus, medulla oblongata, occipital lobe, putamen, substantia nigra, temporal lobe,

HGNC: 18884

OMIM: 607198

KEGG: hsa:55775

STRING: 9606.ENSP00000337353

UniGene: Hs.209945