| Abstract | Mammalian DNA polymerase beta (polB, ) is a 39-kDa protein with both nucleotidyltransferase and 5'-deoxyribose phosphodiesterase activities, playing a role in both excision repair and meiosis. polB has a modular organisation with an 8-kDa N-terminal domain (NTD) connected to the 31-kDa C-terminal domain by a protease-hypersensitive hinge region. The NTD acts as a single-stranded DNA binding domain, interacting most efficiently with the 5'-phosphate of the downstream primer of the gapped DNA. This interaction is mediated by a helix-hairpin-helix motif (HhH), which is also found in several other DNA repair enzymes. The residue threonine 79 (T79), which is located within the NTD, was identified as being critical to polB function, even though it makes no contact with either DNA template or dNTP substrate; T79 is located between two HhH motifs, and acts as a hinge residue that is important for positioning the DNA within the active site [ 12121998].
The catalytic core (residues 148-242) of murine terminal deoxynucleotidyl transferase (TdT, ) displays a structural fold that is similar to polB, and shares a common two-metal ion mechanism of nucleotidyl transfer with polB [11823435]. TdT elongates DNA strands in a template-independent manner, and belongs to the pol X family of polymerases. TdT has only been found in vertebrates, where it is highly conserved. TdT brings additional diversity in the immune repertoire by adding nucleotides, called N regions, to the V(D)J recombination junction sites of immunoglobulin and T-cell receptor genes. |
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