InterPro domain: IPR002008

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 3'-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. Members of family X are small (about 40kDa) compared with other polymerases and encompass two distinct polymerase enzymes that have similar functionality: vertebrate polymerase beta (same as yeast pol 4), and terminal deoxynucleotidyl-transferase (TdT) ( 2.7.7.31 ). The former functions in DNA repair, whilethe latter terminally adds single nucleotides to polydeoxynucleotide chains.Both enzymes catalyse addition of nucleotides in a distributive manner, i.e. theydissociate from the template-primer after addition of each nucleotide.DNA-polymerases show a degree of structural similarity with RNA-polymerases.

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