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Terminal deoxynucleotidyl transferase

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Title: Terminal deoxynucleotidyl transferase  
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Subject: Acute lymphoblastic leukemia, Lymphocytic leukemia, Diffuse infiltrative lymphocytosis syndrome, Primary mediastinal B-cell lymphoma, Large-cell lymphoma
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Terminal deoxynucleotidyl transferase


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

Contents

  • Function 1
  • Uses 2
  • See also 3
  • References 4
  • Further reading 5
  • External links 6

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 that 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]

In immunohistochemistry, antibodies to TdT can be used to demonstrate the presence of immature T and B cells and multipotent haematopoietic stem cells, which possess the antigen, while mature lymphoid cells are always TdT-negative. While TdT-positive cells are found in small numbers in healthy lymph nodes and tonsils, the malignant cells of acute lymphoblastic leukaemia are also TdT-positive, and the antibody can, therefore, be used as part of a panel to diagnose this disease and to distinguish it from, for example, small cell tumours of childhood.[5]

See also

References

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Further reading

External links



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