Affinage

DNTT

DNA nucleotidylexotransferase · UniProt P04053

Length
509 aa
Mass
58.5 kDa
Annotated
2026-04-28
100 papers in source corpus 18 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNTT (TdT) is a template-independent DNA polymerase that adds random (N-region) nucleotides to the 3′-OH ends of V, D, and J gene segments during V(D)J recombination, thereby generating junctional diversity in immunoglobulin and T-cell receptor genes essential for adaptive immunity. TdT-deficient mice completely lack N-region additions and show increased homology-directed joining, while ectopic TdT expression disrupts invariant γδ TCR junctions by introducing random nucleotides, establishing TdT as both necessary and sufficient for N-nucleotide diversification (PMID:8356451, PMID:7584135). TdT transcription is activated by E2A/E47 and repressed by Ikaros (which competes with Ets activators at the TdT promoter during thymocyte maturation) and by c-Myc/Max at the initiator element, while IL-7Rα signaling is required for TdT expression in B-cell progenitors (PMID:8890174, PMID:11459831, PMID:27658954). At the protein level, TdT enzymatic activity is negatively regulated by direct binding partners TdIF1 (which blocks DNA access via the Pol β-like domain) and TReP-132 (which binds the N-terminal region and reduces activity to ~2.5% of maximum), providing post-translational control of N-nucleotide addition during recombination (PMID:17663723, PMID:16371131).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1976 Medium

    Establishing where TdT is expressed — TdT was localized to cortical thymocytes and absent from medullary thymocytes, providing the first cellular context for its function in immature lymphocytes.

    Evidence Density gradient fractionation and immunofluorescence of thymocyte subsets

    PMID:1249420

    Open questions at the time
    • Expression in bone marrow pre-B cells not yet examined
    • Functional consequence of cortical restriction unknown
  2. 1987 High

    Defining the enzymology — TdT was shown to possess distinct substrate (dNTP) and primer (DNA) binding domains through Ap5A inhibition kinetics and UV cross-linking, establishing the biochemical framework for its template-independent polymerase activity.

    Evidence In vitro competitive inhibition kinetics, UV cross-linking, and covalent labeling stoichiometry

    PMID:2439117

    Open questions at the time
    • No structural model at atomic resolution
    • Mechanism of template independence not resolved
  3. 1988 High

    Demonstrating pharmacological vulnerability — TdT was shown to directly mediate selective cytotoxicity of chain-terminating nucleoside analogs (ddA) in TdT-positive cells, using isogenic TdT+/− cell pairs.

    Evidence Retroviral TdT cDNA transduction creating isogenic cell pair, cytotoxicity assays, primary leukemia cell validation

    PMID:2836001

    Open questions at the time
    • In vivo therapeutic relevance not tested
    • Whether other nucleoside analogs exploit TdT similarly was unclear
  4. 1993 High

    Proving the in vivo function — TdT knockout mice completely lacked N-region nucleotide additions at V(D)J junctions in both immunoglobulin and TCR genes, establishing TdT as the sole enzyme responsible for junctional diversity via random nucleotide insertion.

    Evidence TdT-deficient mice generated by gene targeting; V(D)J junction sequencing in two independent studies

    PMID:8356451 PMID:8356452

    Open questions at the time
    • Immune functional consequences (infection susceptibility) of lost N-regions not characterized
    • Compensatory mechanisms for junctional diversity not explored
  5. 1995 High

    Demonstrating sufficiency and competitive mechanism — ectopic TdT expression reduced invariant γδ TCR junctions by introducing N-nucleotides, showing TdT activity actively competes with homology-directed joining; separately, c-Myc/Max was identified as a transcriptional repressor via the TdT initiator element.

    Evidence TdT transgenic mice with V(D)J junction sequencing; EMSA and reporter assays for c-Myc/Max at InrTdT

    PMID:7584135 PMID:7870572

    Open questions at the time
    • How c-Myc repression is developmentally regulated at the TdT locus not determined
    • Relative contribution of transcriptional vs. post-translational control unclear
  6. 1996 Medium

    Identifying upstream transcriptional activators — E2A/E47 was shown to activate endogenous TdT transcription, linking TdT expression to the B-cell developmental transcription factor network.

    Evidence E47 overexpression in fibroblasts and B×T hybrid cell lines with endogenous TdT locus activation by northern blot

    PMID:8890174

    Open questions at the time
    • Direct E2A binding to TdT regulatory elements not demonstrated
    • Whether E2A is required (not just sufficient) for TdT expression in vivo not shown
  7. 2001 High

    Resolving developmental shut-off — Ikaros was shown to silence TdT by competing with Ets activators for promoter occupancy, with chromatin remodeling preceding pericentromeric repositioning during CD4+CD8+ thymocyte differentiation.

    Evidence Binding competition assays, integrated promoter mutation analysis in thymocyte lines, restriction enzyme accessibility

    PMID:11459831

    Open questions at the time
    • Identity of the specific Ets factor activating TdT not resolved
    • Whether Ikaros-mediated silencing is sufficient without additional repressors unknown
  8. 2006 High

    Discovering post-translational negative regulators — TReP-132 was identified as a direct TdT-binding partner that reduces enzymatic activity to ~2.5%, and TdIF1 was subsequently shown to block TdT-DNA access via the Pol β-like domain, together establishing a protein-level regulatory layer for TdT activity.

    Evidence Yeast two-hybrid, co-IP, pull-down, in vitro TdT activity assays with recombinant proteins, domain mapping

    PMID:16371131 PMID:17663723

    Open questions at the time
    • In vivo requirement for TdIF1/TReP-132 in regulating N-nucleotide length not tested
    • Whether TdIF1 and TReP-132 act sequentially or redundantly during V(D)J recombination unknown
    • Structural basis of TdIF1–TdT and TReP-132–TdT interactions not resolved
  9. 2016 Medium

    Linking TdT expression to cytokine signaling — IL-7Rα signaling was found to be required for TdT expression in human B-cell progenitors; IL-7Rα-deficient patients showed reduced TdT and fewer N-nucleotide additions at Dh-Jh junctions.

    Evidence Molecular analysis of human fetal vs. pediatric bone marrow, IL-7Rα-deficient patient cells, IGH junction sequencing

    PMID:27658954

    Open questions at the time
    • Signaling pathway between IL-7Rα and TdT transcription not dissected
    • Whether IL-7Rα regulates TdT transcriptionally or post-transcriptionally not determined
  10. 2022 High

    Redefining TdT as a lineage tracer — TdT reporter mice revealed transient TdT induction on multipotent progenitors (MPPs) before stable upregulation along the lymphoid trajectory, repositioning TdT expression as an early marker of lymphoid specification.

    Evidence Two independent TdT reporter/tracer transgenic mouse lines, single-cell CITE-seq, transplantation, lineage tracing

    PMID:35354960

    Open questions at the time
    • Functional role of TdT in MPPs (if any) beyond lineage marking unknown
    • Signals controlling transient TdT induction in MPPs not identified
  11. 2021 High

    Exploiting TdT as a therapeutic target — TdT-derived peptides were shown to be processed and presented on HLA-A*02:01 on ALL cells, enabling TCR-engineered T cells to selectively kill primary ALL cells in vitro and in vivo while sparing mature lymphocytes.

    Evidence TCR-modified T cell killing assays, three disseminated B-ALL mouse models, humanized mouse experiments

    PMID:34873326

    Open questions at the time
    • Clinical efficacy and safety in humans not tested
    • Whether TdT peptide presentation varies across HLA types not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of TdT's template-independent polymerase mechanism in the context of the RAG recombinase complex, the in vivo roles of TdIF1 and TReP-132 in calibrating N-nucleotide addition length, and the functional significance of transient TdT expression in multipotent progenitors.
  • No high-resolution structure of TdT engaged at a V(D)J coding end in complex with RAG
  • In vivo genetic validation of TdIF1/TReP-132 regulation missing
  • Functional consequence of TdT in MPPs unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 6
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-168256 Immune System 4 GO:0003677 DNA binding 2
Partners
IKZF1TCF3TDIF1TREP-132

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 TdT is responsible for template-independent N-region nucleotide addition at V(D)J junctions; TdT-deficient mice lack N regions in immunoglobulin and T cell receptor variable region genes, and show increased frequency of homology-directed recombination. Genetic knockout (TdT-deficient mice), sequencing of V(D)J junctions Science High 8356451 8356452
1976 TdT is present exclusively (or in markedly higher concentrations) in cortical thymocytes (approximately 65% of cortical thymocytes are TdT-positive) and is absent from medullary thymocytes, as determined by Ficoll gradient fractionation and antigenic/functional marker characterization. Density gradient fractionation, immunofluorescence, functional marker analysis Journal of Immunology Medium 1249420
1987 TdT catalysis is inhibited by Ap5A acting at both the substrate (dNTP) binding domain and the primer (DNA) binding domain; inhibition kinetics and UV cross-linking studies defined two binding sites, and the dissociation constant of the Ap5A-enzyme complex was characterized. In vitro enzymatic assay, competitive inhibition kinetics, UV cross-linking of substrate and primer, oxidized-Ap5A borohydride-reduction binding stoichiometry Biochemistry High 2439117
1995 Short homology (di- or trinucleotide) repeats in coding regions or P elements direct the site of V(D)J recombination and are responsible for invariant gamma-delta TCR junctions; ectopic TdT expression (via CD2 promoter transgene) reduces the frequency of canonical junctions and introduces N nucleotides, demonstrating that TdT activity inhibits junctional homogeneity. Transgenic recombination substrates, TdT transgenic mice, V(D)J junction sequencing Immunity High 7584135
1996 E47 (E2A protein) activates endogenous TdT gene transcription in fibroblasts, demonstrating TdT is a transcriptional target of E2A proteins early in B-cell development. Stable B×T hybrid cell lines, E47 overexpression in fibroblasts, northern blot / transcriptional activation of endogenous TdT locus The EMBO Journal Medium 8890174
1995 c-Myc/myn (Max) protein complex binds the TdT initiator (InrTdT) at the transcription initiation site and represses TdT transcriptional activity when c-Myc is overexpressed. Gel retardation (EMSA), co-transfection/reporter assays, mutagenesis of initiator sequences Nucleic Acids Research Medium 7870572
2001 Ikaros dimers compete with an Ets activator for occupancy of the TdT promoter; Ikaros-binding site mutations abolish TdT down-regulation upon CD4+CD8+ thymocyte differentiation, and chromatin alterations accompany down-regulation preceding pericentromeric repositioning of the inactive gene. Binding/competition assays, integrated promoter mutation analysis in thymocyte lines, restriction enzyme accessibility assay, small Ikaros isoform overexpression Genes & Development High 11459831
1988 2',3'-dideoxyadenosine (ddA) is selectively cytotoxic for TdT-positive cells; a pre-B cell line rendered TdT-positive by retroviral TdT cDNA transduction showed 90% cell death vs. 30% in TdT-negative parental cells, establishing TdT's direct role in mediating ddA/coformycin cytotoxicity via chain-terminating ddAMP additions. Retroviral TdT cDNA transduction, TdT-positive vs. TdT-negative isogenic cell pair, cytotoxicity assay, ex vivo leukemic cell exposure Blood High 2836001
1996 Cordycepin (3'-deoxyadenosine) induces apoptosis selectively in TdT-positive leukemia cells; this is associated with increased protein kinase A (PKA) activity, and in cell-free experiments phosphorylation of TdT by PKA dramatically increases TdT endonuclease activity on supercoiled plasmid DNA, suggesting TdT can act as an apoptotic endonuclease after PKA phosphorylation. Cell cytotoxicity assay, PKA activity measurement, cell-free reconstitution of TdT endonuclease activity with recombinant TdT + PKA Leukemia Medium 8667637
2007 TdT-interacting factor 1 (TdIF1) binds the Pol beta-like region of TdT and blocks TdT access to DNA ends; in the presence of dsDNA, TdIF1 preferentially binds dsDNA and releases TdT, allowing localized TdT activity near AT-rich sequences. TdIF1 contains three DNA-binding regions including an AT-hook-like motif and a helix-turn-helix motif, a bipartite NLS, a TdT-binding region, and a dimerization domain. Yeast two-hybrid, pull-down assay, co-immunoprecipitation, in vitro TdT activity assay with dsDNA, co-localization in COS7 cells, domain deletion/mutation analysis Genes to Cells High 17663723
2006 TReP-132 directly binds TdT through TdT's N-terminal region and reduces TdT enzymatic activity to approximately 2.5% of maximum in vitro; TReP-132 also interacts with TdIF1, and both proteins co-localize with TdT in the nucleus, indicating TdT activity during V(D)J recombination is negatively regulated by TReP-132. Yeast two-hybrid, pull-down assay, co-immunoprecipitation, in vitro TdT activity assay, co-localization in COS7 cells Genes to Cells Medium 16371131
1995 Avian (chicken) TdT is expressed exclusively in the thymus (not bone marrow or bursa of Fabricius), indicating its role is restricted to T-cell receptor diversification and not immunoglobulin gene diversification in birds; the recombinant avian TdT has lower specific activity than mammalian TdTs. cDNA cloning, bacterial recombinant protein expression and purification, enzymatic activity assay, northern blot, RT-PCR of developmental tissues Nucleic Acids Research Medium 7596835
2016 Decreased TdT (and XRCC4) expression in fetal B-cell progenitors results in fewer N-nucleotide additions in IGH rearrangements; IL-7Rα signaling is required for TdT expression, as shown by analysis of IL-7Rα-deficient patients whose progenitor-B cells have reduced TdT expression and fewer N-nucleotide additions at Dh-Jh junctions. Molecular analysis of human fetal vs. pediatric bone marrow B-cell precursors, analysis of IL-7Rα-deficient patient cells, single-cell gene expression, IGH junction sequencing Scientific Reports Medium 27658954
2004 Two TdT isoforms (TdT1 and TdT2, differing by a 57-amino acid deletion including the first helix-hairpin-helix DNA-binding motif) are expressed in the Mexican axolotl; TdT1 contains all conserved structural motifs required for activity. Phylogenetic analysis shows TdT and DNA polymerase mu are closely related and both were present in the common ancestor of jawed vertebrates. cDNA cloning, sequence alignment, phylogenetic analysis, RT-PCR developmental expression profiling Immunogenetics Medium 15146297
2019 NPM1 mutations in AML display hallmarks of TdT-mediated N-nucleotide addition: insertion mutations show G/C-rich N-nucleotide tracts with polypurine/polypyrimidine stacking bias, and recurrent type A, B, D mutations require 1, 2, or 3 N-nucleotide extensions consistent with TdT priming replication slippage. A TdT-mutator model predicts relative incidence of all 256 potential 4-bp insertions (ρ=0.484, P<0.0001). Mutational analysis of 2430 NPM1 mutations, statistical modeling, N-nucleotide composition analysis, comparison of pediatric vs. adult mutation spectra Blood Medium 31650162
2022 Using TdT reporter/tracer transgenic mice, transient TdT induction was detected on a newly identified multipotent progenitor (MPP) subset lacking self-renewal but retaining multilineage differentiation potential; stable, progressive TdT upregulation defines the lymphoid developmental trajectory, and multipotency in TdT+ MPPs is associated with ESAM expression. Two newly generated TdT reporter/tracer transgenic mouse lines, single-cell CITE-seq, transplantation assays, lineage tracing Nature Immunology High 35354960
2021 T cells expressing TCRs specific for TdT-derived peptides presented on HLA-A*02:01 selectively eliminate primary ALL cells (T- and B-cell origin) in vitro and in three mouse models of disseminated B-ALL, while sparing normal peripheral T- and B-cell repertoires, demonstrating TdT peptides are processed and presented as HLA-A*02:01-restricted intracellular antigens on leukemic cells. TCR-modified T cell killing assays in vitro, three disseminated B-ALL mouse models, humanized mouse in vivo experiments, primary ALL cell co-culture Nature Biotechnology High 34873326

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Lack of N regions in antigen receptor variable region genes of TdT-deficient lymphocytes. Science (New York, N.Y.) 383 8356451
1993 Mice lacking TdT: mature animals with an immature lymphocyte repertoire. Science (New York, N.Y.) 367 8356452
2000 DNA polymerase mu (Pol mu), homologous to TdT, could act as a DNA mutator in eukaryotic cells. The EMBO journal 233 10747040
2001 Down-regulation of TDT transcription in CD4(+)CD8(+) thymocytes by Ikaros proteins in direct competition with an Ets activator. Genes & development 123 11459831
1976 The distribution of terminal deoxynucleotidyl transferase (TdT) among subsets of thymocytes in the rat. Journal of immunology (Baltimore, Md. : 1950) 122 1249420
1978 Adenosine deaminase, terminal deoxynucleotidyl transferase (TdT), and cell surface markers in childhood acute leukemia. Blood 115 281253
1985 Human bone marrow cells positive for terminal deoxynucleotidyl transferase (TdT), HLA-DR, and a T cell marker may represent prothymocytes. Journal of immunology (Baltimore, Md. : 1950) 98 2413114
2002 CD56(+) TdT(+) blastic natural killer cell tumor of the skin: a primitive systemic malignancy related to myelomonocytic leukemia. Cancer 93 12015765
1996 E47 activates the Ig-heavy chain and TdT loci in non-B cells. The EMBO journal 87 8890174
2007 TdT expression in Merkel cell carcinoma: potential diagnostic pitfall with blastic hematological malignancies and expanded immunohistochemical analysis. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 85 17885674
2015 Intracellular calcium dynamics in cortical microglia responding to focal laser injury in the PC::G5-tdT reporter mouse. Frontiers in molecular neuroscience 72 26005403
1992 The significance of CD34 and TdT determinations in patients with untreated de novo acute myeloid leukemia. Leukemia 68 1279324
1999 A logistic regression based extension of the TDT for continuous and categorical traits. Annals of human genetics 62 10738544
1984 TdT-positive acute leukemia with monocytoid characteristics: clinical, cytochemical, cytogenetic, and immunologic findings. Blood 61 6733275
1999 Combined sib-TDT and TDT provide evidence for linkage of the interleukin-1 gene cluster to erosive rheumatoid arthritis. Human molecular genetics 60 10441334
1991 A molecular genetic linkage map of mouse chromosome 19, including the lpr, Ly-44, and Tdt genes. Biochemical genetics 60 1684099
2016 Sensitive electrochemical assay of alkaline phosphatase activity based on TdT-mediated hemin/G-quadruplex DNAzyme nanowires for signal amplification. Biosensors & bioelectronics 58 27668724
2005 TDT-association analysis of EKN1 and dyslexia in a Colorado twin cohort. Human genetics 54 16133186
2018 High-grade B-cell lymphomas with TdT expression: a diagnostic and classification dilemma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 52 30181564
1995 The role of short homology repeats and TdT in generation of the invariant gamma delta antigen receptor repertoire in the fetal thymus. Immunity 51 7584135
1995 Further characterisation of the in situ terminal deoxynucleotidyl transferase (TdT) assay for the flow cytometric analysis of apoptosis in drug resistant and drug sensitive leukaemic cells. Cytometry 51 7587710
2016 Target-triggered catalytic hairpin assembly and TdT-catalyzed DNA polymerization for amplified electronic detection of thrombin in human serums. Biosensors & bioelectronics 50 27592241
1997 MIC2, TdT, bcl-2, and CD34 expression in paraffin-embedded high-grade lymphoma/acute lymphoblastic leukemia distinguishes between distinct clinicopathologic entities. Human pathology 48 9343323
2015 A luminescence switch-on probe for terminal deoxynucleotidyl transferase (TdT) activity detection by using an iridium(III)-based i-motif probe. Chemical communications (Cambridge, England) 47 25999030
2008 Reactivity with TdT in Merkel cell carcinoma: a potential diagnostic pitfall. American journal of clinical pathology 47 18480005
1993 Terminal deoxynucleotidyl transferase (TdT) expression in acute myeloid leukemia. Leukemia 47 7688837
1996 Induction of apoptosis by cordycepin in ADA-inhibited TdT-positive leukemia cells. Leukemia 45 8667637
1983 Distinct lymphoblastic and myeloblastic populations in TdT positive acute myeloblastic leukemia: evidence by double-fluorescence staining. Leukemia research 45 6343731
1997 Linkage disequilibrium between the dopamine transporter gene (DAT1) and bipolar disorder: extending the transmission disequilibrium test (TDT) to examine genetic heterogeneity. Genetic epidemiology 43 9433566
2011 Expression of TdT in Merkel cell carcinoma and small cell lung carcinoma. American journal of clinical pathology 42 21571955
2013 Immunohistochemical expression of PAX5 and TdT by Merkel cell carcinoma and pulmonary small cell carcinoma: a potential diagnostic pitfall but useful discriminatory marker. International journal of clinical and experimental pathology 41 23329999
2013 MTHFR C677T polymorphism and risk of congenital heart defects: evidence from 29 case-control and TDT studies. PloS one 41 23536781
1995 The c-myc protein represses the lambda 5 and TdT initiators. Nucleic acids research 41 7870572
1991 Combined flow cytometric assessment of cell surface antigens and nuclear TdT for the detection of minimal residual disease in acute leukaemia. British journal of haematology 39 1998595
1984 A selective culture system for generating terminal deoxynucleotidyl transferase-positive (TdT+) lymphoid precursor cells in vitro. I. Description of the culture system. The Journal of experimental medicine 38 6210337
2014 A TdT-mediated cascade signal amplification strategy based on dendritic DNA matrix for label-free multifunctional electrochemical biosensing. Biosensors & bioelectronics 36 25118111
1988 Translocation (6;9) may be associated with a specific TdT-positive immunological phenotype in ANLL. Leukemia 34 3347092
2022 Mutational Landscape of TdT+ Large B-cell Lymphomas Supports Their Distinction From B-lymphoblastic Neoplasms: A Multiparameter Study of a Rare and Aggressive Entity. The American journal of surgical pathology 33 34392269
2019 Molecular roulette: nucleophosmin mutations in AML are orchestrated through N-nucleotide addition by TdT. Blood 33 31650162
1997 013 (CD99) positivity in hematologic proliferations correlates with TdT positivity. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 33 9110287
2020 Terminal deoxynucleotidyl transferase induced activators to unlock the trans-cleavage of CRISPR/Cpf 1 (TdT-IU- CRISPR/Cpf 1): An ultrasensitive biosensor for Dam MTase activity detection. Biosensors & bioelectronics 30 32568693
1980 A micromethod for determination of terminal deoxynucleotidyl transferase (TdT) in the diagnostic evaluation of acute leukemias. Journal of cancer research and clinical oncology 29 6935216
2022 Dntt expression reveals developmental hierarchy and lineage specification of hematopoietic progenitors. Nature immunology 28 35354960
2021 T cells targeted to TdT kill leukemic lymphoblasts while sparing normal lymphocytes. Nature biotechnology 28 34873326
1988 TdT positive B-cell acute lymphoblastic leukaemia (B-ALL) without Burkitt characteristics. British journal of haematology 28 3288272
2020 An ultrasensitive electrochemical sensing platform for the detection of cTnI based on aptamer recognition and signal amplification assisted by TdT. RSC advances 27 35517933
1986 Improved detection of terminal transferase (TdT): the use of detergents on glutaraldehyde-fixed non-dehydrated cells prevents denaturation and diffusion artifacts. Leukemia research 27 3091949
2007 VEGF C-634G polymorphism is associated with protection from isolated ventricular septal defect: case-control and TDT studies. European journal of human genetics : EJHG 26 17625508
1986 Incidence of TdT positivity in cases of leukemia and lymphoma. Acta haematologica 26 3088880
2000 General equations for Pt, Ps, and the power of the TDT and the affected-sib-pair test. American journal of human genetics 25 11013135
1996 Enhancement of TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method using mung bean nuclease, a single-stranded DNA digestion enzyme. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 25 8609368
2004 Screening of SNPs at 18 positional candidate genes, located within the GD-1 locus on chromosome 14q23-q32, for susceptibility to Graves' disease: a TDT study. Molecular genetics and metabolism 24 15542398
1998 In vivo incidence of apoptosis evaluated with the TdT FragEL DNA fragmentation detection kit in cartilage and bone cells of the rat tibia. Tissue & cell 24 10036787
1996 Repertoires of antigen receptors in Tdt congenitally deficient mice. International reviews of immunology 24 8884428
1987 Regeneration of TdT+, pre-B, and B cells in bone marrow after allogeneic bone marrow transplantation. Transplantation 23 3296354
2019 Downregulation of TdT Expression through Splicing Modulation by Antisense Peptide Nucleic Acid (PNA). Current pharmaceutical biotechnology 22 30727883
1995 Adaptation of the TdT assay for semi-quantitative flow cytometric detection of DNA strand breaks. Cytometry 22 7587711
2018 Purification and functional characterization of the vacuolar malate transporter tDT from Arabidopsis. The Journal of biological chemistry 21 29367340
2017 Progression of liver fibrosis can be controlled by adequate chelation in transfusion-dependent thalassemia (TDT). Annals of hematology 21 28875336
2003 N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) in schizophrenia: TDT and case-control analyses. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 21 12707933
1988 2',3'-Dideoxyadenosine is selectively toxic for TdT-positive cells. Blood 21 2836001
2019 A "signal-on" electrochemical biosensor based on DNAzyme-driven bipedal DNA walkers and TdT-mediated cascade signal amplification strategy. Analytica chimica acta 20 31987151
2005 Lack of evidence of association between MTHFR C677T polymorphism and congenital heart disease in a TDT study design. International journal of cardiology 20 16207540
1987 Multiple chromosome abnormalities in a drug resistant TdT positive B-cell leukemia. Leukemia research 20 3493393
1985 Phenotypic conversion of TdT+ adult AML to CALLA+ ALL. Scandinavian journal of haematology 20 3864234
2020 ExoIII and TdT dependent isothermal amplification (ETDA) colorimetric biosensor for ultra-sensitive detection of Hg2. Food chemistry 19 32045813
2017 In situ formed copper nanoparticles templated by TdT-mediated DNA for enhanced SPR sensor-based DNA assay. Biosensors & bioelectronics 19 28544921
2016 Decreased IL7Rα and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin. Scientific reports 19 27658954
1988 Immunohistochemical staining for terminal deoxynucleotidyl transferase (TDT). An enhanced method in routinely processed formalin-fixed tissue sections. American journal of clinical pathology 19 3258730
2023 Fluorescent aptasensor based on the MNPs-CRISPR/Cas12a-TdT for the determination of nasopharyngeal carcinoma-derived exosomes. Mikrochimica acta 18 36700990
2022 Humanized V(D)J-rearranging and TdT-expressing mouse vaccine models with physiological HIV-1 broadly neutralizing antibody precursors. Proceedings of the National Academy of Sciences of the United States of America 18 36574685
2015 Terminal Deoxynucleotidyl Transferase (TdT)-Mediated dUTP Nick-End Labeling (TUNEL) for Detection of Apoptotic Cells in Drosophila. Cold Spring Harbor protocols 18 26034307
2002 Robust TDT-type candidate-gene association tests. Annals of human genetics 18 12174218
1987 Biochemistry of terminal deoxynucleotidyltransferase (TdT): characterization and mechanism of inhibition of TdT by P1, P5-bis(5'-adenosyl) pentaphosphate. Biochemistry 18 2439117
2002 Characterization of tdt genes for the degradation of tricyclic diterpenes by Pseudomonas diterpeniphila A19-6a. Canadian journal of microbiology 17 11888163
1995 T-cell specific avian TdT: characterization of the cDNA and recombinant enzyme. Nucleic acids research 17 7596835
1983 Paroxysmal nocturnal hemoglobinuria terminating in TdT-positive acute leukemia. American journal of hematology 17 6573126
2021 Mantle cell lymphomas with concomitant MYC and CCND1 breakpoints are recurrently TdT positive and frequently show high-grade pathological and genetic features. Virchows Archiv : an international journal of pathology 16 33528622
2015 On the use of an appropriate TdT-mediated dUTP-biotin nick end labeling assay to identify apoptotic cells. Analytical biochemistry 16 25862087
2007 Identification of functional domains in TdIF1 and its inhibitory mechanism for TdT activity. Genes to cells : devoted to molecular & cellular mechanisms 16 17663723
2006 Evaluation of CD7 and terminal deoxynucleotidyl transferase (TdT) expression in CD34+ myeloblasts from patients with myelodysplastic syndrome. Leukemia research 16 16417922
2004 Early expression of two TdT isoforms in the hematopoietic system of the Mexican axolotl. Implications for the evolutionary origin of the N-nucleotide addition. Immunogenetics 16 15146297
2002 A case of primary cutaneous CD56+, TdT+, CD4+, blastic NK-cell lymphoma in a 19-year-old woman. The American Journal of dermatopathology 16 11803287
1989 Detection of terminal deoxynucleotidyl transferase (TdT) by flow cytometry in leukemic disorders. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 16 2647840
1998 Propidium iodide quenches the fluorescence of TdT-incorporated FITC-labeled dUTP in apoptotic cells. Cytometry 15 9845437
1995 The TDT reveals linkage and linkage disequilibrium in a rare disease. Genetic epidemiology 15 8787986
2019 Terminal deoxynucleotidyl transferase (TdT)-catalyzed homo-nucleotides-constituted ssDNA: Inducing tunable-size nanogap for core-shell plasmonic metal nanostructure and acting as Raman reporters for detection of Escherichia coli O157:H7. Biosensors & bioelectronics 14 31203177
1995 Differential TdT expression in acute leukemia by flow cytometry: a quantitative study. Leukemia 14 7723388
1985 Antigenic phenotype of TdT-positive cells in human peripheral blood. Cellular immunology 14 3155660
2023 A Quenched Size-Expanded Nucleotide Reports Activity of the Leukemia Biomarker Terminal Deoxynucleotidyl Transferase (TdT). Angewandte Chemie (International ed. in English) 13 36880583
1985 A new solid-phase immunoassay for terminal deoxynucleotidyl transferase: analysis of TdT antigen in cells, plasma, and serum. Blood 13 3880644
2018 Simultaneous Monitoring of Cell-surface Receptor and Tumor-targeted Photodynamic Therapy via TdT-initiated Poly-G-Quadruplexes. Scientific reports 12 29615769
2017 Terminal Deoxynucleotidyl Transferase (TdT)-negative Lymphoblastic Leukemia in Pediatric Patients: Incidence and Clinical Significance. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 12 29187045
2006 Direct binding of TReP-132 with TdT results in reduction of TdT activity. Genes to cells : devoted to molecular & cellular mechanisms 12 16371131
1997 Detection of terminal deoxynucleotidyl transferase (TdT) in nonhematopoietic small round cell tumors of children. Pediatric pathology & laboratory medicine : journal of the Society for Pediatric Pathology, affiliated with the International Paediatric Pathology Association 12 9353824
1987 Heterogeneity of TdT+, HLA-DR+ acute leukaemia: immunological, immunocytochemical and clinical evidence of lymphoid and myeloid origin. European journal of haematology 12 3036570
1984 Chronic anemia progressing to Auer rod-positive and TdT-positive acute leukemia with 5q- chromosomal anomaly. American journal of hematology 12 6093506
2012 Incorporating genotype uncertainties into the genotypic TDT for main effects and gene-environment interactions. Genetic epidemiology 11 22678881
1990 TdT-Positive, SmIg-Negative B Precursor Cell Leukemia with Burkitt Morphology: A Case Report. Leukemia & lymphoma 11 27456743
2022 CD117, BAP1, MTAP, and TdT Is a Useful Immunohistochemical Panel to Distinguish Thymoma from Thymic Carcinoma. Cancers 10 35565429