InterPro domain: IPR002054

DNA carries the biological information that instructs cells how to existin an ordered fashion: accurate replication is thus one of the mostimportant events in the cell life cycle. This function is mediated byDNA-directed DNA-polymerases, which add nucleotide triphosphate (dNTP)residues to the 5'-end of the growing DNA chain, using a complementary DNA as template. Small RNA molecules are generally used as primers forchain elongation, although terminal proteins may also be used. Three motifs, A, B and C [ 1 ], are seen to be conserved across all DNA-polymerases, with motifs A and C also seen in RNA- polymerases. They are centred on invariant residues, and their structural significance was implied from the Klenow (Escherichia coli) structure: motif A contains a strictly-conserved aspartate at the junction of a beta-strand and an alpha-helix; motif B contains an alpha-helix with positive charges; and motif C has a doublet of negative charges, located in a beta-turn-beta secondary structure [ 2 ].

DNA polymerases ( 2.7.7.7 ) can be classified, on the basis of sequencesimilarity [ 2 , 3 ], into at least four different groups: A, B, C and X. X family polymerases fill in short gaps during DNA repair, and are small (about 40kDa) compared with other polymerases. They are relatively inaccurate enzymes and play roles in base excision repair, in non-homologous end joining (NHEJ) which acts mainly to repair damage due to ionizing radiation, and in V(D)J recombination [ 3 , 4 ]. X family polymerases include eukaryotic Pol beta, Pol lambda, Pol mu and terminal deoxynucleotidyl-transferase (TdT) ( 2.7.7.31 ). Pol beta and Pol lambda are primarily DNA template-dependent polymerases, whereas TdT is a DNA template-independent polymerase [ 5 ]. Pol mu has both template dependent and template independent activities [ 6 ]. These enzymes catalyse addition of nucleotides in a distributive manner, i.e. they dissociate from the template-primer after addition of each nucleotide.DNA-polymerases show a degree of structural similarity with RNA-polymerases.

This domain is found either at the extreme N or C termini of DNA polymerase X proteins.

1. An attempt to unify the structure of polymerases. Protein Eng. 3, 461-7
2. Bacteriophage PRD1 DNA polymerase: evolution of DNA polymerases. Proc. Natl. Acad. Sci. U.S.A. 84, 8287-91
3. A gradient of template dependence defines distinct biological roles for family X polymerases in nonhomologous end joining. Mol. Cell 19, 357-66
4. Mutational analysis of terminal deoxynucleotidyltransferase-mediated N-nucleotide addition in V(D)J recombination. J. Immunol. 172, 5478-88
5. Template-independent DNA polymerases. Curr Protoc Mol Biol Chapter 3, Unit3.6
6. Structural insight into the substrate specificity of DNA Polymerase mu. Nat. Struct. Mol. Biol. 14, 45-53