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Terminal deoxynucleotidyl transferase information


DNTT
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesDNTT, TDT, DNA nucleotidylexotransferase, Terminal deoxynucleotidyl transferase
External IDsOMIM: 187410 MGI: 98659 HomoloGene: 3014 GeneCards: DNTT
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001017520
NM_004088

NM_001043228
NM_009345

RefSeq (protein)

NP_001017520
NP_004079

NP_001036693
NP_033371

Location (UCSC)Chr 10: 96.3 – 96.34 MbChr 19: 41.02 – 41.05 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Terminal deoxynucleotidyl transferase (TdT), also known as DNA nucleotidylexotransferase (DNTT) or terminal transferase, is a specialized DNA polymerase expressed in immature, pre-B, pre-T lymphoid cells, and acute lymphoblastic leukemia/lymphoma cells. TdT adds N-nucleotides to the V, D, and J exons of the TCR and BCR genes during antibody gene recombination, enabling the phenomenon of junctional diversity. In humans, terminal transferase is encoded by the DNTT gene.[5][6] As a member of the X family of DNA polymerase enzymes, it works in conjunction with polymerase λ and polymerase μ, both of which belong to the same X family of polymerase enzymes. The diversity introduced by TdT has played an important role in the evolution of the vertebrate immune system, significantly increasing the variety of antigen receptors that a cell is equipped with to fight pathogens. Studies using TdT knockout mice have found drastic reductions (10-fold) in T-cell receptor (TCR) diversity compared with that of normal, or wild-type, systems. The greater diversity of TCRs that an organism is equipped with leads to greater resistance to infection.[7][8] Although TdT was one of the first DNA polymerases identified in mammals in 1960,[9] it remains one of the least understood of all DNA polymerases.[7] In 2016–18, TdT was discovered to demonstrate in trans template dependant behaviour in addition to its more broadly known template independent behaviour[10][11]

TdT is absent in fetal liver HSCs, significantly impairing junctional diversity in B-cells during the fetal period.[12]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000107447 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025014 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Isobe M, Huebner K, Erikson J, Peterson RC, Bollum FJ, Chang LM, Croce CM (September 1985). "Chromosome localization of the gene for human terminal deoxynucleotidyltransferase to region 10q23-q25". Proceedings of the National Academy of Sciences of the United States of America. 82 (17): 5836–40. Bibcode:1985PNAS...82.5836I. doi:10.1073/pnas.82.17.5836. PMC 390648. PMID 3862101.
  6. ^ Yang-Feng TL, Landau NR, Baltimore D, Francke U (1986). "The terminal deoxynucleotidyltransferase gene is located on human chromosome 10 (10q23----q24) and on mouse chromosome 19". Cytogenetics and Cell Genetics. 43 (3–4): 121–6. doi:10.1159/000132309. PMID 3467897.
  7. ^ a b Motea EA, Berdis AJ (May 2010). "Terminal deoxynucleotidyl transferase: the story of a misguided DNA polymerase". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1804 (5): 1151–66. doi:10.1016/j.bbapap.2009.06.030. PMC 2846215. PMID 19596089.
  8. ^ Haeryfar SM, Hickman HD, Irvine KR, Tscharke DC, Bennink JR, Yewdell JW (July 2008). "Terminal deoxynucleotidyl transferase establishes and broadens antiviral CD8+ T cell immunodominance hierarchies". Journal of Immunology. 181 (1): 649–59. doi:10.4049/jimmunol.181.1.649. PMC 2587314. PMID 18566432.
  9. ^ Bollum FJ (August 1960). "Calf thymus polymerase". The Journal of Biological Chemistry. 235 (8): 2399–403. doi:10.1016/S0021-9258(18)64634-4. PMID 13802334.
  10. ^ Gouge J, Rosario S, Romain F, Poitevin F, Béguin P, Delarue M (April 2015). "Structural basis for a novel mechanism of DNA bridging and alignment in eukaryotic DSB DNA repair". The EMBO Journal. 34 (8): 1126–42. doi:10.15252/embj.201489643. PMC 4406656. PMID 25762590.
  11. ^ Loc'h J, Delarue M (December 2018). "Terminal deoxynucleotidyltransferase: the story of an untemplated DNA polymerase capable of DNA bridging and templated synthesis across strands" (PDF). Current Opinion in Structural Biology. 53: 22–31. doi:10.1016/j.sbi.2018.03.019. PMID 29656238. S2CID 4882661.
  12. ^ Hardy R (2008). "Chapter 7: B Lymphocyte Development and Biology". In Paul W (ed.). Fundamental Immunology (Book) (6th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 237–269. ISBN 978-0-7817-6519-0.

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such as Pol σ (sigma), Pol λ (lambda), Pol μ (mu), and Terminal deoxynucleotidyl transferase (TdT). Family X polymerases are found mainly in vertebrates...

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TDT

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palindromic, 'P' nucleotides. Subsequent to this, the enzyme, terminal deoxynucleotidyl transferase (TdT), adds further random 'N' nucleotides. The newly synthesised...

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cytometry. In the malignant lymphoblasts of ALL, expression of terminal deoxynucleotidyl transferase (TdT) on the cell surface can help differentiate malignant...

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have explored the possibility of enzymatic synthesis using terminal deoxynucleotidyl transferase (TdT), a DNA polymerase that requires no template. However...

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activity and mechanism of action of cordycepin against terminal deoxynucleotidyl transferase-positive (TdT+) leukemic cells". Biochemical Pharmacology...

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described the DNA fragmentation assay based on the use of the terminal deoxynucleotidyl transferase (TUNEL) which become one of the standard methods to detect...

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of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations". Proceedings of the National...

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XDNA

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they have a reduced geometric constraint for substrates. Terminal deoxynucleotidyl transferase (TdT) has been used previously to synthesize strands of...

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DNA polymerase mu

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the double-strand break. Pol μ is also closely related to terminal deoxynucleotidyl transferase (TdT), a specialized DNA polymerase that adds random nucleotides...

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Krause JR, Brody JP, Kaplan SS, Penchansky L (June 1986). "Terminal deoxynucleotidyl transferase activity in acute leukemia: a study of 100 cases comparing...

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Artemis complex

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magnesium-containing buffers). Nucleotides are added at the open ends by terminal deoxynucleotidyl transferase (TdT). This occurs until there are complementary sequences...

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processing, X family DNA polymerases (Pol μ and Pol λ) and terminal deoxynucleotidyl transferase (TdT) for DNA synthesis, and the XLF/XRCC4/LigIV complex...

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