Specialised DNA polymerases in Escherichia coli: roles within multiple pathways.

Abstract

In many bacterial species, DNA damage triggers the SOS response; a pathway that regulates the production of DNA repair and damage tolerance proteins, including error-prone DNA polymerases. These specialised polymerases are capable of bypassing lesions in the template DNA, a process known as translesion synthesis (TLS). Specificity for lesion types varies considerably between the different types of TLS polymerases. TLS polymerases are mainly described as working in the context of replisomes that are stalled at lesions or in lesion-containing gaps left behind the replisome. Recently, a series of single-molecule fluorescence microscopy studies have revealed that two TLS polymerases, pol IV and pol V, rarely colocalise with replisomes in Escherichia coli cells, suggesting that most TLS activity happens in a non-replisomal context. In this review, we re-visit the evidence for the involvement of TLS polymerases in other pathways. A series of genetic and biochemical studies indicates that TLS polymerases could participate in nucleotide excision repair, homologous recombination and transcription. In addition, oxidation of the nucleotide pool, which is known to be induced by multiple stressors, including many antibiotics, appears to favour TLS polymerase activity and thus increases mutation rates. Ultimately, participation of TLS polymerases within non-replisomal pathways may represent a major source of mutations in bacterial cells and calls for more extensive investigation.