Property Summary

NCBI Gene PubMed Count 58
PubMed Score 126.53
PubTator Score 90.16

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (10)

Disease log2 FC p
cutaneous lupus erythematosus 1.300 5.8e-04
psoriasis 1.300 7.9e-04
osteosarcoma -1.005 8.5e-05
group 3 medulloblastoma 1.200 3.8e-04
atypical teratoid / rhabdoid tumor 1.200 7.0e-07
medulloblastoma, large-cell 1.300 5.7e-06
tuberculosis and treatment for 3 months -1.300 3.0e-05
non-small cell lung cancer 1.136 4.6e-15
lung cancer 2.900 9.2e-06
Breast cancer 1.100 9.6e-06

Gene RIF (45)

PMID Text
26421495 Tyrosyl-DNA-phosphodiesterase I (TDP1) participates in the removal and repair of stabilized-Top2alpha cleavage complexes in human cells.
26181362 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.
26121557 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.
25987486 both TOP1 and TDP1 were upregulated in the tumor tissue compared to the adjacent non-tumor tissue in non-small cell lung cancer tissue
25841101 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.
25609251 These findings suggest that the flexibility of Tdp1 active site residues may impair the resolution of mutant Tdp1 covalent phosphohistidyl intermediates
25522766 varying expression levels of TOP1 and TDP1 polypeptides in multiple colorectal cancer cell lines and in clinical colorectal cancer samples, are reported.
24856239 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
24355542 Data provides insights into the possible inactivation of TDP1 in cancers and its relationship to cellular response to Top1-targeted drugs.
24335147 TDP1 deficiency sensitizes human cells to base damage, independently of apurinic/apyrimidinic endonuclease I (APE1).
24183900 Results show Tdp1 catalyzes hydrolysis of apurinic/apyrimidinic site analog correlates with the DNA helix distortion induced by the substituent.
24161509 TDP1 and APTX take part in the mitochondrial DNA repair and are apparently being transported from the cell nucleus. (Review)
23913164 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
23852793 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
23536040 These studies suggest that one role of cytoplasmic Tdp1 is the repair of mitochondrial DNA lesions arising from oxidative stress.
22415824 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
22375014 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.
22155078 Analysis of the active-site mechanism of tyrosyl-DNA phosphodiesterase I.
21628532 topoisomerase 1, tyrosyl-DNA phosphodiesterase 1, and single-strand break repair modulate transcription-dependent CAG repeat contractions
21276450 Study investigates substrate specificity of Tdp1; data suggest a role for Tdp1 in a new APE-independent base excision repair pathway.
21041670 These findings provide evidence for TDP1 as a novel mitochondrial enzyme.
20097655 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.
20009512 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.
19851285 TDP1 phosphorylation at serine residue 81 promotes cell survival and DNA repair in response to carnitine O-palmitoyltransferase-induced DNA double-strand breaks.
19604089 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19505854 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.
18347181 Observational study of gene-disease association and pharmacogenomic / toxicogenomic. (HuGE Navigator)
18270339 Observational study and meta-analysis of gene-disease association. (HuGE Navigator)
17948061 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.
17707402 Data show that mutation of a conserved active site residue converts tyrosyl-DNA phosphodiesterase I into a DNA topoisomerase I-dependent poison.
17600775 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
16935573 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
16775218 TDP1 has a role in DNA single-strand break repair and neurodegeneration [review]
16141202 Tdp1 may function to remove a variety of 3' adducts from DNA during DNA repair
15920477 inhibitors of Tdp1 could act synergistically with camptothecin in anticancer therapy
15811850 Tdp1 only acts upon double strand breaks in vivo
15647511 The role of TDP1 in 3'-phosphoglycolate processing during in vitro end joining of DNA double-strand breaks.
15494395 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
15248776 conserved sequences and amino acids important for catalytic activity and enzyme specificity were identified
12470949 We report the three-dimensional structures of human Tdp1 bound to the phosphate transition state analogs vanadate and tungstate
12244316 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
12023295 a role for hTdp1 in repair of free radical-mediated DNA double strand breaks bearing terminally blocked 3' overhangs.
11839309 1.69 A crystal structure of human tyrosyl-DNA phosphodiesterase
11572945 Protein assay of expressed FLJ11090 shows that it encodes human tyrosyl-DNA phodphodiesterase (TDP1).
10521354 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.

AA Sequence

MSQEGDYGRWTISSSDESEEEKPKPDKPSTSSLLCARQGAANEPRYTCSEAQKAAHKRKISPVKFSNTDS      1 - 70
VLPPKRQKSGSQEDLGWCLSSSDDELQPEMPQKQAEKVVIKKEKDISAPNDGTAQRTENHGAPACHRLKE     71 - 140
EEDEYETSGEGQDIWDMLDKGNPFQFYLTRVSGVKPKYNSGALHIKDILSPLFGTLVSSAQFNYCFDVDW    141 - 210
LVKQYPPEFRKKPILLVHGDKREAKAHLHAQAKPYENISLCQAKLDIAFGTHHTKMMLLLYEEGLRVVIH    211 - 280
TSNLIHADWHQKTQGIWLSPLYPRIADGTHKSGESPTHFKADLISYLMAYNAPSLKEWIDVIHKHDLSET    281 - 350
NVYLIGSTPGRFQGSQKDNWGHFRLKKLLKDHASSMPNAESWPVVGQFSSVGSLGADESKWLCSEFKESM    351 - 420
LTLGKESKTPGKSSVPLYLIYPSVENVRTSLEGYPAGGSLPYSIQTAEKQNWLHSYFHKWSAETSGRSNA    421 - 490
MPHIKTYMRPSPDFSKIAWFLVTSANLSKAAWGALEKNGTQLMIRSYELGVLFLPSAFGLDSFKVKQKFF    491 - 560
AGSQEPMATFPVPYDLPPELYGSKDRPWIWNIPYVKAPDTHGNMWVPS                          561 - 608
//

Text Mined References (62)

PMID Year Title
26421495 2015 Tyrosyl-DNA-phosphodiesterase I (TDP1) participates in the removal and repair of stabilized-Top2? cleavage complexes in human cells.
26181362 2015 Poly(ADP-ribose)polymerase 1 stimulates the AP-site cleavage activity of tyrosyl-DNA phosphodiesterase 1.
26121557 2015 A Theoretical Study of Phosphoryl Transfers of Tyrosyl-DNA Phosphodiesterase I (Tdp1) and the Possibility of a "Dead-End" Phosphohistidine Intermediate.
25987486 2015 Correlation between topoisomerase I and tyrosyl-DNA phosphodiesterase 1 activities in non-small cell lung cancer tissue.
25841101 2015 TDP1 promotes assembly of non-homologous end joining protein complexes on DNA.
25609251 2015 Tyrosyl-DNA phosphodiesterase I catalytic mutants reveal an alternative nucleophile that can catalyze substrate cleavage.
25522766 2015 Clinical and cellular roles for TDP1 and TOP1 in modulating colorectal cancer response to irinotecan.
24856239 2014 Tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2).
24355542 2014 Epigenetic and genetic inactivation of tyrosyl-DNA-phosphodiesterase 1 (TDP1) in human lung cancer cells from the NCI-60 panel.
24335147 2014 TDP1 deficiency sensitizes human cells to base damage via distinct topoisomerase I and PARP mechanisms with potential applications for cancer therapy.
24183900 2013 The mechanism of human tyrosyl-DNA phosphodiesterase 1 in the cleavage of AP site and its synthetic analogs.
24161509 2014 The role of TDP1 and APTX in mitochondrial DNA repair.
23913164 2013 TDP1 and PARP1 deficiency are cytotoxic to rhabdomyosarcoma cells.
23852793 2013 Association of tyrosyl-DNA phosphodiesterase 1 polymorphism with Tourette syndrome in Taiwanese patients.
23536040 2013 Expression profile and mitochondrial colocalization of Tdp1 in peripheral human tissues.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22822062 2012 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.
22415824 2012 SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair.
22375014 2012 Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs DNA damage induced by topoisomerases I and II and base alkylation in vertebrate cells.
22155078 2012 Analysis of the active-site mechanism of tyrosyl-DNA phosphodiesterase I: a member of the phospholipase D superfamily.
21628532 2011 Topoisomerase 1 and single-strand break repair modulate transcription-induced CAG repeat contraction in human cells.
21276450 2011 AP-site cleavage activity of tyrosyl-DNA phosphodiesterase 1.
21269460 2011 Initial characterization of the human central proteome.
21041670 2010 Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria.
20097655 2010 The DNA binding and 3'-end preferential activity of human tyrosyl-DNA phosphodiesterase.
20009512 2010 TDP1 serine 81 promotes interaction with DNA ligase IIIalpha and facilitates cell survival following DNA damage.
19851285 2009 Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA-PK.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19604089 2009 Pharmacodynamic genes do not influence risk of neutropenia in cancer patients treated with moderately high-dose irinotecan.
19505854 2009 Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18347181 2008 Irinotecan pharmacogenetics: influence of pharmacodynamic genes.
18270339 2008 Comprehensive analysis of DNA repair gene variants and risk of meningioma.
17948061 2007 Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation?
17707402 2007 Mutation of a conserved active site residue converts tyrosyl-DNA phosphodiesterase I into a DNA topoisomerase I-dependent poison.
17600775 2007 TDP1 facilitates repair of ionizing radiation-induced DNA single-strand breaks.
17576665 2007 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.
17118488 2007 Increased expression and activity of repair genes TDP1 and XPF in non-small cell lung cancer.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16935573 2006 Hereditary ataxia SCAN1 cells are defective for the repair of transcription-dependent topoisomerase I cleavage complexes.
16775218 2006 TDP1-dependent DNA single-strand break repair and neurodegeneration.
16141202 2005 Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages.
15920477 2005 SCAN1 mutant Tdp1 accumulates the enzyme--DNA intermediate and causes camptothecin hypersensitivity.
15811850 2005 Substrate specificity of tyrosyl-DNA phosphodiesterase I (Tdp1).
15744309 2005 Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1.
15647511 2005 Deficiency in 3'-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1).
15494395 2004 TDP1 overexpression in human cells counteracts DNA damage mediated by topoisomerases I and II.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15248776 2004 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.
15111055 2004 Analysis of human tyrosyl-DNA phosphodiesterase I catalytic residues.
14761185 2004 Explorations of peptide and oligonucleotide binding sites of tyrosyl-DNA phosphodiesterase using vanadate complexes.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12618186 2003 Crystal structure of a transition state mimic for Tdp1 assembled from vanadate, DNA, and a topoisomerase I-derived peptide.
12508121 2003 The DNA sequence and analysis of human chromosome 14.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12470949 2002 Insights into substrate binding and catalytic mechanism of human tyrosyl-DNA phosphodiesterase (Tdp1) from vanadate and tungstate-inhibited structures.
12244316 2002 Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy.
12023295 2002 Conversion of phosphoglycolate to phosphate termini on 3' overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1.
11839309 2002 The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1.
11572945 2001 The tyrosyl-DNA phosphodiesterase Tdp1 is a member of the phospholipase D superfamily.
10521354 1999 Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.