Conserved Site

DNA-directed DNA polymerase, family A, conserved site (IPR019760)

Short name: DNA-dir_DNA_pol_A_CS


DNA carries the biological information that instructs cells how to exist in an ordered fashion: accurate replication is thus one of the most important events in the cell life cycle. This function is mediated by DNA-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 for chain elongation, although terminal proteins may also be used. Three motifs, A, B and C [PMID: 2196557], 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 [PMID: 2196557].

DNA polymerases (EC: can be classified, on the basis of sequence similarity [PMID: 3479792, PMID: 2196557], into at least four different groups: A, B, C and X. Members of family X are small (about 40 kDa) 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) (EC: The former functions in DNA repair, while the latter terminally adds single nucleotides to polydeoxynucleotide chains. Both 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.

Five regions of similarity are found in all the polymerases of this entry. The signature of this entry is to the conserved region, known as 'motif B' [PMID: 2196557]; motif B is located in a domain which, in E. coli polA, has been shown to bind deoxynucleotide triphosphate substrates; it contains a conserved tyrosine which has been shown, by photo-affinity labelling, to be in the active site; a conserved lysine, also part of this motif, can be chemically labelled, using pyridoxal phosphate.

GO terms

Biological Process

GO:0006260 DNA replication

Molecular Function

GO:0003887 DNA-directed DNA polymerase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns