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Terminal deoxynucleotidyl transferase (TdT) is a specialized DNA polymerase unique to vertebrates, primarily expressed in immature, pre-B and pre-T lymphoid cells[2][3][6]. Unlike other DNA polymerases, it catalyzes the addition of deoxynucleotides to the 3' hydroxyl termini of DNA strands in a template-independent manner, critically contributing to junctional diversity during V(D)J recombination in lymphocyte antigen receptor genes[1][3][4][6]. TdT belongs to the pol X family of DNA polymerases, characterized by a DNA polymerase β-like fold, and operates by a two-metal-ion catalytic mechanism[1][3][4]. It features a unique "lariat-like" loop that sterically prohibits binding to a DNA template strand, distinguishing its activity from template-dependent polymerases[3][6]. Biomedically, TdT serves primarily as a diagnostic marker for acute lymphoblastic leukemia and related malignancies[3][6]. While not a direct target of current therapeutics, it is essential for normal adaptive immunity, and abnormal expression is implicated in leukemogenesis[3][6].
Inhibition of template-independent DNA elongation; Modulation of V(D)J recombination (experimentally)
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