The DNA polymerases are divided into seven families based on their sequence homology and crystal structure analysis. These include families A, B, C, D, X, Y and RT.
Some of the characteristics of the different families include:
Polymerases in this family are classed as either replicative polymerases or repair polymerases. When DNA is replicated, replicative polymerases match free nucleotides to sequences in template DNA. This coupling of nucleotide bases always occurs in certain combinations, with cytosine always paired to guanine and adenine always paired to thymine.
The repair polymerases “proofread” the new strands created and rectify any mistakes in the base pairing. In this way, the integrity of the original DNA strand that is passed onto daughter cells is preserved.
The replicative members of family A include the T7 DNA polymerase as well as the eukaryotic mitochondrial DNA polymerase γ. The repair polymerases include DNA pol I from E. coli, pol I from Thermus aquaticus and pol I from Bacillus stearothermophilus.
This family mainly contains replicative polymerases that are involved in processing DNA replication during cell division. Many of the polymerases in this family are present in fungi, plants and some are present in bacteriophages. These enzymes contribute to synthesis of both the leading and lagging DNA strands during replication. Family B polymerases are highly accurate in their function and perform 3'-5' proofreading of newly synthesized DNA in order to correct any errors that occur during DNA replication.
Family C polymerases are the major replicative polymerases in bacteria. DNA polymerase III is the main family C polymerase involved in E.coli DNA replication. Polymerase III is made up of the clamp-loading complex, the beta sliding clamp processivity factor and the pol III core. The core comprises three subunits – the α subunit which is the polymerase activity hub, the δ subunit which is the exonucleolytic proofreader, and the θ subunit which may stabilize δ. The core and the beta sliding clamp are present in duplicate, to allow for processing of both the leading and lagging DNA strands.
These polymerases are present in Euryarchaeota, a subdomain of archaea, and are mainly replicative. This family of polymerases is not clearly defined but studies of Pyrococcus furiosus DNA polymerase II suggest this enzyme is a replicative polymerase.
This family includes the eukaryotic polymerase pol β, along with others such as pol μ, pol λ, pol σ and terminal deoxynucleotidyl transferase. Polymerase β performs short patch repair of damaged DNA by fixing alkylated, oxidized or abasic sites that have formed due to DNA damage.
Pol λ and pol μ are involved in the rejoining of breaks that have occurred in double strands of DNA due to hydrogen peroxide (in the case of pol λ) and ionizing radiation (in the case of pol μ). Terminal deoxynucleotidyl transferase is only found in lymphoid tissue and adds non-templated nucleotides at V(D)J junctions, to provide diversity.
These polymerases have a low fidelity for intact DNA strands and are capable of replicating damaged DNA.
One example of a family Y polymerase is pol IV, an error-prone polymerase that has no 3’ to 5’ proofreading activity and is involved in mutagenesis. The enzyme is expressed by a gene (dinB) that is switched on when polymerases stall at the replication fork. This interferes with the processivity of pol III which acts as a checkpoint, stopping replication and allowing time for DNA to be repaired. Cells that lack dinB are at an increased risk of developing mutations caused by agents that damage DNA.
Pol V also belongs to the Y family of polymerases and allows DNA damage to be bypassed in order for replication to continue.
This is the family of reverse transcriptases, which includes eukaryotic telomerases and the reverse transcriptases found in retroviruses. These enzymes work by using RNA as template to synthesize a DNA strand.