DNA nucleotidylexotransferase

DNA nucleotidylexotransferase (DNTT), also known as terminal deoxynucleotidyl transferase (TdT), is an enzyme that plays a crucial role in the development of the immune system. This enzyme is a template-independent DNA polymerase, meaning it adds nucleotides to the 3' end of a DNA strand without needing a template strand. It is specifically involved in the process of V(D)J recombination, which generates the diverse array of antibodies and T cell receptors necessary for the adaptive immune response.

Function[edit | edit source]

DNTT is expressed primarily in lymphoid tissue, including the thymus and bone marrow, where lymphocytes are developed. During V(D)J recombination, DNTT adds random nucleotides to the DNA segments being joined, contributing to the diversity of the antigen receptors. This process is essential for the adaptive immune system to recognize a wide range of pathogens.

Clinical Significance[edit | edit source]

Mutations or alterations in the expression of DNTT can lead to immunodeficiencies or increased susceptibility to certain diseases. For example, a deficiency in DNTT activity can result in a reduced repertoire of antibodies and T cell receptors, compromising the immune response. Conversely, aberrant activity of DNTT has been associated with certain types of leukemia and lymphoma, where it may contribute to the uncontrolled proliferation of lymphocytes.

Structure[edit | edit source]

DNTT is a member of the X family of DNA polymerases. Its structure includes several domains critical for its enzymatic activity, including a polymerase domain and a nucleotidyltransferase domain. The enzyme requires a divalent metal ion, typically magnesium or manganese, for its activity.

Research and Applications[edit | edit source]

Research on DNTT has provided insights into the mechanisms of immune system development and the etiology of certain immune disorders and cancers. Additionally, DNTT has applications in biotechnology and molecular biology, such as adding poly(A) tails to DNA fragments for cloning purposes.