DNA polymerase mu (POLM)

DNA polymerase mu (POLM) is a multifunctional enzyme in the X family of DNA polymerases, encoded by the human POLM gene[1][2]. It plays a central role in the repair of DNA double-strand breaks through the nonhomologous end joining (NHEJ) pathway, acting as a gap-filling polymerase that can operate with minimal template guidance and can even add nucleotides in a template-independent manner, especially at DNA ends with low complementarity[1][2][5]. POLM is structurally and functionally related to both DNA polymerase lambda (Pol λ) and terminal deoxynucleotidyl transferase (TdT). Unique among DNA polymerases, POLM can add bases to blunt ends during NHEJ and participates specifically in V(D)J recombination for generating light chain diversity in B and T lymphocytes[1]. It is highly expressed in lymphoid tissues and has been implicated in both the generation of immune diversity and the promotion of genomic instability due to its error-prone DNA synthesis activity, especially in the presence of manganese ions[2][3][5]. Mutations or dysregulation of POLM have been linked to increased mutation rates, tumor formation, and possible roles in immune function and cancer[2][5]. Currently, there are no approved drugs targeting POLM, and therapeutic modulation would require caution due to potential effects on DNA repair fidelity and immune diversity.

Other names

DNA-directed DNA/RNA polymerase mupolmuPol MuTdt-NTerminal transferasePol iotaPOLMpolymerase (DNA) mupolymerase (DNA-directed), muterminal transferase

Not applicable for current drugs (there are no approved drugs known to directly inhibit or modulate DNA polymerase mu).