100
lagging strand synthesis [3]. Pol I is the most abundant polymerase accounting for
>95 % of polymerase activity in E. coli, yet cells lacking pol I have been found,
suggesting that pol I activity can be replaced by the other four polymerases. Pol I
adds ~15–20 nucleotides per second, thus showing poor processivity. Instead, pol I
starts adding nucleotides at the RNA primer–template junction known as the origin
of replication (ori). Approximately ~ 400 bp downstream from the origin, the pol III
holoenzyme is assembled and takes over replication at a highly processive speed
and nature [12].
Pol γ, encoded by the polG gene, is the only mitochondrial DNA polymerase
and therefore replicates and repairs mitochondrial DNA. In addition, pol γ has
proofreading 3′–5′ exonuclease (like the other A-member polymerases) and 5′ dRP
lyase activities. Any mutation that leads to a limited or non-functioning pol γ has
significant effect on mtDNA and is the most common cause of autosomal inherited
mithochondrial disorders (pol γ contains a C-terminus polymerase domain and a
N-terminus 3′–5′ exonuclease domain that are connected via the linker region binding the accessory subunit. The accessory subunit binds DNA and is required for the
proccessivity of pol γ. Point mutation A467T in the linker region is responsible for
more than one third of all pol γ-associated mitochondrial disorders [13].
While a lot of pol θ homologs, encoded by the polQ genes, are found in eukaryotes, their functions are not clearly understood. The sequence of amino acids in the
C-terminus is what classifies pol θ as family A polymerase, although the error rate
for pol θ is more closely related to family Y polymerases. pol θ may extend the
mismatched primer termini and can bypass abasic sites by adding a nucleotide opposite the lesion.
Among viral members of A family, one should mention the T3 and T5 DNA
polymerases that provide the replication of DNA of those viruses.
4.2.2.2 Family B
This polymerase family includes enzymes with the highest level of replication fidelity. It is clearly understood that the members of this family are actually the main
catalysts of DNA replication in viruses, archea and eukaryotes. Functions of bacterial B DNA polymerases are more complicated.
The DNA polymerase II (pol II) is the most known bacterial B-family polymerase. It is coded by polB gene and has 3′–5′ exonuclease activity [14]. Pol II participates in the DNA repair and replication restart to bypass lesions. Its cell presence
can vary from 30 to 50 copies per cell to 200–300 during SOS induction. Pol II is
also thought to be a backup to pol III as it can interact with holoenzyme proteins and
assumes a high level of processivity. The special role of pol II is thought to be the
ability to direct polymerase activity at the replication fork and its help to the stalled
pol III in bypassing terminal mismatches [14].
Eukaryotic family B DNA pols (α, δ, ε and ζ) are multisubunit enzymes which,
with the exception of the DNA pol ζ, are responsible for the replication of nuclear
DNA in all eukaryotic organisms.
A. Yu. Nyporko
lagging strand synthesis [3]. Pol I is the most abundant polymerase accounting for
>95 % of polymerase activity in E. coli, yet cells lacking pol I have been found,
suggesting that pol I activity can be replaced by the other four polymerases. Pol I
adds ~15–20 nucleotides per second, thus showing poor processivity. Instead, pol I
starts adding nucleotides at the RNA primer–template junction known as the origin
of replication (ori). Approximately ~ 400 bp downstream from the origin, the pol III
holoenzyme is assembled and takes over replication at a highly processive speed
and nature [12].
Pol γ, encoded by the polG gene, is the only mitochondrial DNA polymerase
and therefore replicates and repairs mitochondrial DNA. In addition, pol γ has
proofreading 3′–5′ exonuclease (like the other A-member polymerases) and 5′ dRP
lyase activities. Any mutation that leads to a limited or non-functioning pol γ has
significant effect on mtDNA and is the most common cause of autosomal inherited
mithochondrial disorders (pol γ contains a C-terminus polymerase domain and a
N-terminus 3′–5′ exonuclease domain that are connected via the linker region binding the accessory subunit. The accessory subunit binds DNA and is required for the
proccessivity of pol γ. Point mutation A467T in the linker region is responsible for
more than one third of all pol γ-associated mitochondrial disorders [13].
While a lot of pol θ homologs, encoded by the polQ genes, are found in eukaryotes, their functions are not clearly understood. The sequence of amino acids in the
C-terminus is what classifies pol θ as family A polymerase, although the error rate
for pol θ is more closely related to family Y polymerases. pol θ may extend the
mismatched primer termini and can bypass abasic sites by adding a nucleotide opposite the lesion.
Among viral members of A family, one should mention the T3 and T5 DNA
polymerases that provide the replication of DNA of those viruses.
4.2.2.2 Family B
This polymerase family includes enzymes with the highest level of replication fidelity. It is clearly understood that the members of this family are actually the main
catalysts of DNA replication in viruses, archea and eukaryotes. Functions of bacterial B DNA polymerases are more complicated.
The DNA polymerase II (pol II) is the most known bacterial B-family polymerase. It is coded by polB gene and has 3′–5′ exonuclease activity [14]. Pol II participates in the DNA repair and replication restart to bypass lesions. Its cell presence
can vary from 30 to 50 copies per cell to 200–300 during SOS induction. Pol II is
also thought to be a backup to pol III as it can interact with holoenzyme proteins and
assumes a high level of processivity. The special role of pol II is thought to be the
ability to direct polymerase activity at the replication fork and its help to the stalled
pol III in bypassing terminal mismatches [14].
Eukaryotic family B DNA pols (α, δ, ε and ζ) are multisubunit enzymes which,
with the exception of the DNA pol ζ, are responsible for the replication of nuclear
DNA in all eukaryotic organisms.
A. Yu. Nyporko