DNA Damage Response and Translesion Synthesis in Prokaryotic Systems

The DNA damage response in bacteria encompasses a coordinated network of lesion detection, signal transduction and lesion tolerance pathways that safeguard genome integrity under stress. Following DNA damage from environmental agents or replication errors, single‐stranded DNA accumulates and triggers the formation of RecA nucleoprotein filaments. RecA activates the SOS regulon by promoting autocleavage of the LexA repressor, leading to upregulation of excision repair enzymes, recombination factors and specialised translesion synthesis (TLS) polymerases. TLS polymerases, often of the Y‐family or atypical C‐family, bypass lesions that stall the high‐fidelity DNA polymerase III holoenzyme by inserting nucleotides opposite damaged bases or reinitiating synthesis downstream of lesions. Key players include DNA polymerase IV (DinB), polymerase V (UmuD′2C) and mutasome complexes comprising ImuA, ImuB and DnaE2 in certain species. These enzymes interact transiently with the β clamp to access primer–template junctions and trade places with the replicative polymerase in a tightly regulated manner to limit mutagenesis. The balance between accurate repair and lesion bypass underpins prokaryotic survival, adaptation and the emergence of antibiotic resistance, highlighting the global significance of TLS in bacterial evolution and biotechnology applications such as strain engineering and antimicrobial design.

Research from Nature Portfolio

Studies in Mycobacterium species have delineated distinct contributions of TLS polymerases to mutation spectra under stress. Overexpression of a DinB1 homologue was shown to drive rifampicin‐resistance through characteristic missense mutations, while also catalysing −1 frameshift events in homopolymeric tracts. DnaE2 and DinBs act redundantly to mediate damage‐induced frameshift mutagenesis, whereas DinB1 predominates in spontaneous frameshifts. These findings reveal polymerase‐specific mutational signatures that collectively fuel genome diversification, with direct implications for the evolution of drug resistance and host adaptation in pathogenic bacteria.

DNA Damage Response and Translesion Synthesis in Prokaryotic Systems publication trend

The graph below shows the total number of articles in dna damage response and translesion synthesis in prokaryotic systems across all publications each year (not limited to Nature Index journals).

Technical terms

RecA: A recombinase that binds single‐stranded DNA to form a nucleoprotein filament, signalling SOS induction and facilitating homologous recombination.

SOS response: A global transcriptional programme induced by DNA damage that upregulates repair, recombination and TLS pathways.

Translesion synthesis (TLS): A damage‐tolerance mechanism in which specialised polymerases synthesize DNA directly across lesions, permitting replication to continue at the expense of fidelity.

β clamp: A ring‐shaped accessory protein that encircles DNA and tethers polymerases to the replication fork, coordinating polymerase switching.

Mutasome: A multi‐protein complex assembled in response to damage, typically comprising accessory factors and a TLS polymerase such as DnaE2 or UmuC.

References

1. The RecA-NT homology motif in ImuB mediates the interaction with ImuA′, which is essential for DNA damage–induced mutagenesis. Journal of Biological Chemistry (2024).
2. Regulation of Mutagenic DNA Polymerase V Activation in Space and Time. PLOS Genetics (2015).
3. New insights into the structures and interactions of bacterial Y-family DNA polymerases. Nucleic Acids Research (2019).
4. Replisome-mediated Translesion Synthesis and Leading Strand Template Lesion Skipping Are Competing Bypass Mechanisms*. Journal of Biological Chemistry (2014).
5. Distinctive roles of translesion polymerases DinB1 and DnaE2 in diversification of the mycobacterial genome through substitution and frameshift mutagenesis. Nature Communications (2022).
6. Multiple Strategies for Translesion Synthesis in Bacteria. Cells (2012).