Terminal deoxynucleotidyl transferase

DNA nucleotidylexotransferase
Amino acids 19-125 of human DNA nucleotidylexotransferase. PDB rendering based on 2coe.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2COE
Identifiers
Symbols	DNTT ; TDT
External IDs	OMIM: 187410 MGI: 98659 HomoloGene: 3014 ChEMBL: 4810 GeneCards: DNTT Gene
EC number	2.7.7.31
Gene ontology Molecular function • DNA binding • DNA-directed DNA polymerase activity • DNA nucleotidylexotransferase activity • protein binding • metal ion binding Cellular component • nucleus • nucleoplasm • cytoplasm Biological process • DNA metabolic process • DNA modification • DNA biosynthetic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1791	21673
Ensembl	ENSG00000107447	ENSMUSG00000025014
UniProt	P04053	P09838
RefSeq (mRNA)	NM_001017520	NM_001043228
RefSeq (protein)	NP_001017520	NP_001036693
Location (UCSC)	Chr 10: 96.3 – 96.34 Mb	Chr 19: 41.03 – 41.06 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.

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

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.

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.

See also

• DNA
• DNA polymerase

External links

• Terminal Deoxyribonucleotidyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)