Mechanisms of Homologous Recombination in Bacterial DNA Repair

Homologous recombination constitutes a fundamental mechanism by which bacteria safeguard genomic integrity in the face of double‐strand breaks and replication‐fork stalling. The process is initiated by detection of DNA lesions and processing of broken ends by specialised helicase–nuclease complexes, most notably RecBCD in γ‐proteobacteria or its analogue AddAB in other species. Following end resection, single‐stranded 3′ overhangs are stabilised by single‐strand DNA‐binding proteins and subsequently bound by the RecA recombinase, which catalyses strand invasion into an undamaged homologous duplex. This presynaptic filament searches for sequence homology and mediates DNA pairing and exchange, forming a displacement loop (D‐loop). Resolution of Holliday junction intermediates by resolvases restores intact chromosomes. The entire pathway is tightly regulated by sequence motifs such as Chi sites, which modulate enzyme activity to favour recombinational repair over degradation, and coordinated by accessory factors that ensure timely loading of RecA and resolution of recombination intermediates. Collectively, these steps enable error‐free repair, maintain genetic stability and contribute to adaptability under stress.

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Technical terms

Homologous recombination: A high‐fidelity repair process that exchanges genetic information between similar DNA sequences.

Double‐strand break (DSB): A lesion involving discontinuities in both strands of the DNA helix.

RecBCD complex: A multifunctional helicase–nuclease that recognises and processes DSBs to generate recombinogenic 3′ overhangs.

Chi site: An octameric DNA sequence that alters RecBCD activity to promote RecA loading and recombination.

RecA protein: A recombinase that forms filaments on single‐stranded DNA and catalyses strand invasion into homologous duplex regions.

Helicase–nuclease: An enzyme complex combining DNA‐unwinding (helicase) and DNA‐cleaving (nuclease) activities to process DNA ends.

References

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2. Structural basis for the inhibition of RecBCD by Gam and its synergistic antibacterial effect with quinolones. eLife (2016).
3. Mechanism for nuclease regulation in RecBCD. eLife (2016).