Terminal deoxynucleotidyl transferase

Terminal deoxynucleotidyl transferase
Deoxynucleotidyltransferase, terminal

Amino acids 19-125 of human DNA nucleotidylexotransferase. PDB rendering based on 2coe.
Identifiers
Symbols DNTT; TDT
External IDs OMIM187410 MGI98659 HomoloGene3014 GeneCards: DNTT Gene
EC number 2.7.7.31
Orthologs
Species Human Mouse
Entrez 1791 21673
Ensembl ENSG00000107447 ENSMUSG00000025014
UniProt P04053 P09838
RefSeq (mRNA) NM_001017520.1 NM_009345
RefSeq (protein) NP_001017520.1 NP_001036693
Location (UCSC) Chr 10:
98.06 – 98.1 Mb
Chr 19:
41.1 – 41.13 Mb
PubMed search [1] [2]

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 during antibody gene recombination enabling the phenomenon of junctional diversity. In humans, terminal transferase is encoded by the DNTT gene.[1][2]

TdT is notably absent in fetal liver HSCs significantly impairing junctional diversity in B-cells during the fetal period.[3]

Contents

Function

TdT catalyses the addition of nucleotides to the 3' terminus of a DNA molecule. Unlike most DNA polymerases it does not require a template. The preferred substrate of this enzyme is a 3'-overhang, but it can also add nucleotides to blunt or recessed 3' ends. Cobalt is a necessary cofactor, however the enzyme catalyzes reaction upon Mg and Mn administration in vitro.

Uses

Terminal transferase has applications in molecular biology. It can be used in RACE to add nucleotides which can then be used as a template for a primer in subsequent PCR. It can also be used to add nucleotides labeled with radioactive isotopes, for example in the TUNEL assay (Terminal deoxynucleotidyl transferase dUTP Nick End Labeling) for the demonstration of apoptosis (which is marked, in part, by fragmented DNA).

Also used in the immunofluorescence assay for the diagnosis of acute lymphoblastic leukemia.[4]

See also

References

  1. ^ 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". Proc. Natl. Acad. Sci. U.S.A. 82 (17): 5836–40. doi:10.1073/pnas.82.17.5836. PMC 390648. PMID 3862101. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=390648. 
  2. ^ 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". Cytogenet. Cell Genet. 43 (3-4): 121–6. doi:10.1159/000132309. PMID 3467897. 
  3. ^ Hardy, Richard (2008). "Chapter 7: B Lymphocyte Development and Biology". In Paul, William (Book). Fundamental Immunology (6th ed.). Philidelphia, PA: Lippincott Williams & Wilkins. pp. 237–269. ISBN 0-7817-6519-6. 
  4. ^ Faber J, Kantarjian H, Roberts MW, Keating M, Freireich E, Albitar M (January 2000). "Terminal deoxynucleotidyl transferase-negative acute lymphoblastic leukemia". Arch. Pathol. Lab. Med. 124 (1): 92–7. PMID 10629138. 

Further reading

External links

2.7.6: diphosphotransferase
(P2O7) 2.7.7: nucleotidyltransferase
(PO4-nucleoside) 2.7.8: miscellaneous 2.7.10-2.7.13: protein kinase
(PO4; protein acceptor)
B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6

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