Multiple strategies for translesion synthesis in bacteria

Abstract

Damage to DNA is common and can arise from numerous environmental and endogenous sources. In response to ubiquitous DNA damage, Y-family DNA polymerases are induced by the SOS response and are capable of bypassing DNA lesions. In Escherichia coli, these Y-family polymerases are DinB and UmuC, whose activities are modulated by their interaction with the polymerase manager protein UmuD. Many, but not all, bacteria utilize DinB and UmuC homologs. Recently, a C-family polymerase named ImuC, which is similar in primary structure to the replicative DNA polymerase DnaE, was found to be able to copy damaged DNA and either carry out or suppress mutagenesis. ImuC is often found with proteins ImuA and ImuB, the latter of which is similar to Y‑family polymerases, but seems to lack the catalytic residues necessary for polymerase activity. This imuAimuBimuC mutagenesis cassette represents a widespread alternative strategy for translesion synthesis and mutagenesis in bacteria. Bacterial Y‑family and ImuC DNA polymerases contribute to replication past DNA damage and the acquisition of antibiotic resistance.

Figure 1

Some characteristic configurations of the imuABC mutagenesis cassette are shown below. The plethora of imuABC operons has been characterized extensively [183,190,195]. While P. putida and S. meliloti have imuA, imuB, and imuC together as one operon, M. tuberculosis contains imuC separated from imuA and imuB, as well as imuA' instead of imuA.

Figure 2

Percent identities by ClustalW2 [213,214] for the ImuA protein and related proteins. “(p)” represents the plasmid gene product, “(c)” represents the chromosomal gene product. The accessions are from Uniprot [215], from left to right: P0A7C2, P0A154, P0AFZ5, P0A7G6, Q07447, P42443, C1D2C5, C1CXY5, C1D2K8, Q9A3J1, Q6MQS4, Q50730, Q88I84, Q9I5Q0, Q92ZJ8, Q92LA5.

Figure 3

Percent identities by ClustalW2 [213,214] for ImuB protein and related proteins. “(p)” represents the plasmid gene product, “(c)” represents the chromosomal gene product. The accessions are from Uniprot [215] with the exception of D. ficus ImuB from RefSeq [216], from left to right: Q47155, Q9A5I1, B8H428, O50419, C1D2K9, ADO33718, Q88I83, Q9I5Q1, Q92ZJ7, Q92JS7, Q6MQS5.

Figure 4

Percent identities by ClustalW2 [213,214] for ImuC proteins and related proteins. “(p)” represents the plasmid gene product, “(c)” represents the chromosomal gene product. The accessions are from Uniprot [215] with the exception of D. ficus ImuC from RefSeq [216], from left to right: P10443, B8GWS6, Q9XDH5, B8H427, Q6MQS6, O50399, C1D2L1, ADO33730, Q9S291, Q88I82, Q9I5Q2, Q92ZJ6, Q92LA6.