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Gene Review

Dntt  -  deoxynucleotidyltransferase, terminal

Mus musculus

Synonyms: BB160593, DNA nucleotidylexotransferase, TDT, Tdt, Terminal addition enzyme, ...
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Disease relevance of Dntt


High impact information on Dntt

  • Silencing was nucleated at the Dntt promoter by the ordered deacetylation of histone H3 at Lys9 (H3-Lys9), loss of methylation at H3-Lys4 and acquisition of methylation at H3-Lys9, followed by bidirectional spreading of each event [6].
  • Transcription of the lymphocyte-specific terminal deoxynucleotidyltransferase gene begins at a single nucleotide, but no TATA box is present [7].
  • Deficiency in cells expressing terminal transferase in autoimmune (motheaten) mice [8].
  • To test whether the absence of Tdt is essential, we generated Tg mice that express Tdt and add N regions in fetal B cells [9].
  • During variable/diversity/joining (V[D]J) recombination, the enzyme terminal deoxynucleotidyl transferase (Tdt) adds random nucleotides at the junctions of the rearranging gene segments, increasing diversity of the antibody (Ab) and T cell receptor repertoires [10].

Chemical compound and disease context of Dntt


Biological context of Dntt

  • Whereas the TdtS transgene was shown to have functional consequences on the antiphosphorylcholine (PC) B cell repertoire, TdtL Tg mice exhibit a normal PC response, and Tdt(-/)- mice actually exhibit an increase in the PC response and in TEPC 15 idiotype(+) Ab production [10].
  • The inability of TdT to accommodate a template strand can be explained by steric hindrance at the catalytic site caused by a long lariat-like loop, which is absent in DNA polymerase beta [14].
  • Treated mice were evaluated for renal Fas protein and mRNA expression, tissue histopathology, and apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining [15].
  • Analysis of cultures after growth factor deprivation, however, revealed a strikingly accelerated rate of cell death in c-abl mutant cells, due to apoptosis as confirmed by terminal deoxynucleotidyltransferase-mediated UTP nick end labeling analysis [16].
  • N-region insertions, which are characteristic of adult junctional diversity, are obtained at high frequency upon transfection of a terminal deoxynucleotidyltransferase expression vector together with Rag1 and Rag2 [17].

Anatomical context of Dntt


Associations of Dntt with chemical compounds


Regulatory relationships of Dntt


Other interactions of Dntt


Analytical, diagnostic and therapeutic context of Dntt

  • By screening plaques with anti-terminal transferase antibody, positive clones were identified of which some had beta-galactosidase-cDNA fusion proteins identifiable after electrophoretic fractionation by immunoblotting with anti-terminal transferase antibody [1].
  • Chromosomal assignment of the gene coding for human TdT was accomplished by in situ hybridization of a 3H-labeled cDNA probe to human chromosome preparations and by Southern blot analysis of somatic cell hybrid DNAs [21].
  • Particularly informative was UV photofootprinting, using terminal transferase-dependent PCR and nonradioactive detection [33].
  • The cellular and subcellular distribution of terminal deoxynucleotidyl transferase (DNA nucleotidylexotransferase; nucleosidetriphosphate:DNA deoxynucleotidylexotransferase, EC in thymocytes and peripheral lymphocytes from rat, mouse, and calf was studied by immunofluorescence using rabbit antiserum to homogeneous transferase from calf [34].
  • After 2 h of ischemia and 48 h of reperfusion, cortical infarct volume was reduced by 55%, and the density of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive cells was decreased by 36% compared with wild type [35].


  1. Cloning of terminal transferase cDNA by antibody screening. Landau, N.R., St John, T.P., Weissman, I.L., Wolf, S.C., Silverstone, A.E., Baltimore, D. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  2. Comparison of the two murine terminal [corrected] deoxynucleotidyltransferase terminal isoforms. A 20-amino acid insertion in the highly conserved carboxyl-terminal region modifies the thermosensitivity but not the catalytic activity. Boulé, J.B., Rougeon, F., Papanicolaou, C. J. Biol. Chem. (2000) [Pubmed]
  3. Terminal deoxynucleotidyltransferase deficiency decreases autoimmune disease in diabetes-prone nonobese diabetic mice and lupus-prone MRL-Fas(lpr) mice. Robey, I.F., Peterson, M., Horwitz, M.S., Kono, D.H., Stratmann, T., Theofilopoulos, A.N., Sarvetnick, N., Teyton, L., Feeney, A.J. J. Immunol. (2004) [Pubmed]
  4. Isolation and characterization of bovine and mouse terminal deoxynucleotidyltransferase cDNAs expressible in mammalian cells. Koiwai, O., Yokota, T., Kageyama, T., Hirose, T., Yoshida, S., Arai, K. Nucleic Acids Res. (1986) [Pubmed]
  5. Yersinia-induced apoptosis in vivo aids in the establishment of a systemic infection of mice. Monack, D.M., Mecsas, J., Bouley, D., Falkow, S. J. Exp. Med. (1998) [Pubmed]
  6. Dynamic assembly of silent chromatin during thymocyte maturation. Su, R.C., Brown, K.E., Saaber, S., Fisher, A.G., Merkenschlager, M., Smale, S.T. Nat. Genet. (2004) [Pubmed]
  7. The "initiator" as a transcription control element. Smale, S.T., Baltimore, D. Cell (1989) [Pubmed]
  8. Deficiency in cells expressing terminal transferase in autoimmune (motheaten) mice. Landreth, K.S., McCoy, K., Clagett, J., Bollum, F.J., Rosse, C. Nature (1981) [Pubmed]
  9. Increased junctional diversity in fetal B cells results in a loss of protective anti-phosphorylcholine antibodies in adult mice. Benedict, C.L., Kearney, J.F. Immunity (1999) [Pubmed]
  10. The long isoform of terminal deoxynucleotidyl transferase enters the nucleus and, rather than catalyzing nontemplated nucleotide addition, modulates the catalytic activity of the short isoform. Benedict, C.L., Gilfillan, S., Kearney, J.F. J. Exp. Med. (2001) [Pubmed]
  11. DNA polymerase mu (Pol mu), homologous to TdT, could act as a DNA mutator in eukaryotic cells. Domínguez, O., Ruiz, J.F., Laín de Lera, T., García-Díaz, M., González, M.A., Kirchhoff, T., Martínez-A, C., Bernad, A., Blanco, L. EMBO J. (2000) [Pubmed]
  12. Neuroprotective effects of prostaglandin E2 or cAMP against microglial and neuronal free radical mediated toxicity associated with inflammation. Kim, E.J., Kwon, K.J., Park, J.Y., Lee, S.H., Moon, C.H., Baik, E.J. J. Neurosci. Res. (2002) [Pubmed]
  13. Rifampicin attenuates brain damage in focal ischemia. Yulug, B., Kilic, U., Kilic, E., Bähr, M. Brain Res. (2004) [Pubmed]
  14. Crystal structures of a template-independent DNA polymerase: murine terminal deoxynucleotidyltransferase. Delarue, M., Boulé, J.B., Lescar, J., Expert-Bezançon, N., Jourdan, N., Sukumar, N., Rougeon, F., Papanicolaou, C. EMBO J. (2002) [Pubmed]
  15. Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury. Hamar, P., Song, E., Kökény, G., Chen, A., Ouyang, N., Lieberman, J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  16. Increased sensitivity to apoptotic stimuli in c-abl-deficient progenitor B-cell lines. Dorsch, M., Goff, S.P. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  17. Three lymphoid-specific factors account for all junctional diversity characteristic of somatic assembly of T-cell receptor and immunoglobulin genes. Kallenbach, S., Doyen, N., Fanton d'Andon, M., Rougeon, F. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  18. Monoclonal antibodies to human terminal transferase. Bollum, F.J., Augl, C., Chang, L.M. J. Biol. Chem. (1984) [Pubmed]
  19. Expression of apoptosis-related proteins in experimental coxsackievirus myocarditis. Colston, J.T., Chandrasekar, B., Freeman, G.L. Cardiovasc. Res. (1998) [Pubmed]
  20. Acute cigarette smoke exposure induces apoptosis of alveolar macrophages. Aoshiba, K., Tamaoki, J., Nagai, A. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  21. The terminal deoxynucleotidyltransferase gene is located on human chromosome 10 (10q23----q24) and on mouse chromosome 19. Yang-Feng, T.L., Landau, N.R., Baltimore, D., Francke, U. Cytogenet. Cell Genet. (1986) [Pubmed]
  22. Murine pro-B cells require IL-7 and its receptor complex to up-regulate IL-7R alpha, terminal deoxynucleotidyltransferase, and c mu expression. Wei, C., Zeff, R., Goldschneider, I. J. Immunol. (2000) [Pubmed]
  23. Apoptosis in congestive heart failure induced by viral myocarditis in mice. Yamada, T., Matsumori, A., Wang, W.Z., Ohashi, N., Shiota, K., Sasayama, S. Heart and vessels. (1999) [Pubmed]
  24. Paradoxical action of fulvestrant in estradiol-induced regression of tamoxifen-stimulated breast cancer. Osipo, C., Gajdos, C., Liu, H., Chen, B., Jordan, V.C. J. Natl. Cancer Inst. (2003) [Pubmed]
  25. An antitumour lectin from the edible mushroom Agrocybe aegerita. Zhao, C., Sun, H., Tong, X., Qi, Y. Biochem. J. (2003) [Pubmed]
  26. Abrogation of cisplatin-induced programmed cell death in human breast cancer cells by epidermal growth factor antisense RNA. Dixit, M., Yang, J.L., Poirier, M.C., Price, J.O., Andrews, P.A., Arteaga, C.L. J. Natl. Cancer Inst. (1997) [Pubmed]
  27. Activated caspase-1 is not a central mediator of inflammation in the course of ischemia-reperfusion. Daemen, M.A., Denecker, G., van't Veer, C., Wolfs, T.G., Vandenabeele, P., Buurman, W.A. Transplantation (2001) [Pubmed]
  28. Role of endogenous Fas (CD95/Apo-1) ligand in balloon-induced apoptosis, inflammation, and neointima formation. Matter, C.M., Chadjichristos, C.E., Meier, P., von Lukowicz, T., Lohmann, C., Schuler, P.K., Zhang, D., Odermatt, B., Hofmann, E., Brunner, T., Kwak, B.R., Lüscher, T.F. Circulation (2006) [Pubmed]
  29. Smad3 deficiency attenuates renal fibrosis, inflammation,and apoptosis after unilateral ureteral obstruction. Inazaki, K., Kanamaru, Y., Kojima, Y., Sueyoshi, N., Okumura, K., Kaneko, K., Yamashiro, Y., Ogawa, H., Nakao, A. Kidney Int. (2004) [Pubmed]
  30. Retinoid-related orphan receptor gamma (RORgamma) is essential for lymphoid organogenesis and controls apoptosis during thymopoiesis. Kurebayashi, S., Ueda, E., Sakaue, M., Patel, D.D., Medvedev, A., Zhang, F., Jetten, A.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  31. Resistance of differentiating spermatogonia to radiation-induced apoptosis and loss in p53-deficient mice. Hasegawa, M., Zhang, Y., Niibe, H., Terry, N.H., Meistrich, M.L. Radiat. Res. (1998) [Pubmed]
  32. Use of terminal transferase-dependent antisense RNA amplification to determine the transcription start site of the Snrpn gene in individual neurons. Buettner, V.L., LeBon, J.M., Gao, C., Riggs, A.D., Singer-Sam, J. Nucleic Acids Res. (2000) [Pubmed]
  33. Chromatin fine structure profiles for a developmentally regulated gene: reorganization of the lysozyme locus before trans-activator binding and gene expression. Kontaraki, J., Chen, H.H., Riggs, A., Bonifer, C. Genes Dev. (2000) [Pubmed]
  34. Demonstration of terminal deoxynucleotidyl transferase in thymocytes by immunofluorescence. Goldschneider, I., Gregoire, K.E., Barton, R.W., Bollum, F.J. Proc. Natl. Acad. Sci. U.S.A. (1977) [Pubmed]
  35. Caspase activation and neuroprotection in caspase-3- deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation. Le, D.A., Wu, Y., Huang, Z., Matsushita, K., Plesnila, N., Augustinack, J.C., Hyman, B.T., Yuan, J., Kuida, K., Flavell, R.A., Moskowitz, M.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
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