Polymerase fidelity is an important factor in maintaining the integrity of the genome, ensuring that a faithful copy of the template strand is produced. DNA polymerase III is the primary polymerase used in prokaryotes.
Pol III has an exonuclease domain to cleave off any erroneous nucleotides that are incorporated into the DNA strand, removing errors while they are easier to correct. However, some errors are left in, and occasionally there is an issue with the template DNA strand preventing high fidelity polymerase from being able to replicate it.
Trans-lesion and lesion bypass polymerases (DNA polymerase IV and V) are used where DNA polymerase III is unable to replicate. This could be because of a nucleotide isomer being present, inducing polymerase III to detach.
DNA polymerase IV and V have a more forgiving structure, able to cope with conformational changes more easily. Although this allows them to overcome issues in the DNA template, it also increases the chance of errors being introduced. These polymerases are also used in the SOS response (a DNA repair pathway induced during cell stress, such as exposure to a mutagen or high levels of errors during DNA replication), and so are able to translocate very quickly. Although they are more likely to introduce errors, they dissociate from the template strand very quickly. At this point, during normal DNA replication, DNA polymerase III reattaches and continues translocating – overcoming the issue that prevented it from replicated that locus.
Due to the risk of introducing errors and mutations into the DNA while using DNA polymerase IV and V, DNA repair pathways are also used. Enzymes translocate along the nascent dsDNA strand, checking for errors and initiating repair where necessary. This helps maintain genome integrity.