Disease relevance of DNTT

• Terminal deoxynucleotidyltransferase is an enzyme which has been found to be associated with thymus cells, bone marrow cells, as well as leukocytes from patients with acute lymphoblastic leukemia and chronic myelocytic leukemia in blast crisis [1].
• Stereospecificity of human DNA polymerases alpha, beta, gamma, delta and epsilon, HIV-reverse transcriptase, HSV-1 DNA polymerase, calf thymus terminal transferase and Escherichia coli DNA polymerase I in recognizing D- and L-thymidine 5'-triphosphate as substrate [2].
• Recombinant hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) was reported to possess terminal transferase (TNTase) activity, the ability to add nontemplated nucleotides to the 3' end of viral RNAs [3].
• Terminal transferase-like activity in human melanoma cells [4].
• The insoluble primers are tested for their priming efficiency using polynucleotide nucleotidyltransferase from Micrococcus luteus and DNA nucleotidylexotransferase from calf thymus [5].

High impact information on DNTT

• The two forms of TdT therefore have distinct and opposite functions in lymphocyte development [6].
• Increasing TdT expression continuing into adult life results in N region addition and diversification of the T and B cell repertoires [6].
• A search of the translated sequence of the 939-base-pair insert shows three regions beginning after arginine that have greater than 90% homology with the sequence determined from the calf thymus terminal transferase peptides [7].
• A cDNA of the human terminal deoxynucleotidyltransferase (TdT; "terminal transferase," EC 2.7.7.31) was isolated from a human lymphoblastoid cell cDNA library in lambda gt 11 by using immunological procedures [7].
• Exposure of bovine aortic endothelial cells or myocytes to submicromolar levels of DOX induced significant apoptosis as measured by DNA fragmentation and terminal deoxynucleotidyltransferase-mediated nick-end labeling assays [8].

Biological context of DNTT

• The specificity of dTTP cross-linking at the substrate binding site in TdT is demonstrated by the competitive inhibition of the cross-linking reaction by other deoxynucleoside triphosphates, and ATP and its analogues, requiring concentrations consistent with their kinetic constants [9].
• Further proteolytic digestion of the tryptic peptide-dTTP complex, using V8 protease, yielded a smaller peptide, and its analysis narrowed the substrate binding domain to 14 amino acids corresponding to residues 224-237 in the primary amino acid sequence of TdT [9].
• The bovine TdT cDNA clone contains an open reading frame coding for 520 amino acids, Mr 59,678 [10].
• A 58-kDa monomer of terminal transferase was isolated from calf thymus using a monoclonal antibody affinity column [11].
• The phosphorylation and phosphonylation of the 3'-hydroxyl of oligodeoxynucleotide 3'-termini (oligodeoxynucleotidyl kinase activity) catalyzed by calf thymus terminal deoxynucleotidyl transferase (TDT) are discussed [12].

Anatomical context of DNTT

• The cloned TdT cDNA hybridized with poly A+ RNAs of 2,100 b and 3,300 b from stable T-cell leukemia Molt3 and Molt4 cells [13].
• The TdT cDNA was transfected into COS7 monkey fibroblasts directed the synthesis of enzymatically active protein of Mr 59,495 [13].
• In this report, we present evidence that TNTase activity is an inherent function of HCV and bovine viral diarrhea virus RdRps highly purified from both prokaryotic and eukaryotic cells [3].
• In situ terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) staining of lymphoid tissues (pharyngeal tonsil, cervical, retropharyngeal, and inguinal) was used to detect apoptotic cells [14].

Associations of DNTT with chemical compounds

• Furthermore, 2 cysteine residues, Cys-227 and Cys-234, within this domain were found to be involved in the cross-linking of dTTP, suggesting their participation in the process of substrate binding in TdT [9].
• Biochemistry of terminal deoxynucleotidyltransferase. Affinity labeling and identification of the deoxynucleoside triphosphate binding domain of terminal deoxynucleotidyltransferase [9].
• TdT-60 fractionates with terminal transferase during phosphocellulose chromatography and sediments with it in a sucrose gradient [15].
• Terminal transferase from calf thymus accepts nicotinamide mononucleoside 5'-triphosphate as a substrate and efficiently adds one residue to the 3'-end of an oligodeoxynucleotide [16].
• 2'-Deoxy-6-thioguanosine 5'-triphosphate as a substrate for purified human DNA polymerases and calf thymus terminal deoxynucleotidyltransferase in vitro [17].

Other interactions of DNTT

• A sensitive TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay and an antibody that detects cleaved caspase-3 were used to identify apoptotic cells in TG [18].

Analytical, diagnostic and therapeutic context of DNTT

• The alpha and beta polypeptides of photolabeled terminal transferase were resolved by high-performance liquid chromatography [19].
• Analysis of photolabeled peptides from terminal transferase alpha beta using DEAE-cellulose chromatography followed by reverse-phase HPLC confirmed that the photolabeled species were peptides B26 and B27 [19].
• Molecular cloning of human terminal deoxynucleotidyltransferase [7].
• Three peptides isolated by HPLC from tryptic digests of succinylated 58-kDa calf thymus terminal transferase were sequenced, providing 20, 18, and 22 residues of peptide sequence [7].
• An oligo(dT)-purified preparation of calf terminal transferase competed with only the Mr = 58,000 peptide in the immunoprecipitation reaction [20].

References