SOS response pathway (SOS response)

The SOS response is a global regulatory network in bacteria that is activated in response to significant DNA damage, such as that caused by the mutagenic heterocyclic amine Trp-P-1 (3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole) (Sugimura et al., 1977, PNAS). This pathway is primarily controlled by two key proteins: LexA, a repressor that keeps SOS genes silenced under normal conditions, and RecA, which senses DNA damage by binding to single-stranded DNA (Baharoglu & Mazel, 2014, Nature Reviews Microbiology). Upon activation, RecA facilitates the autocatalytic cleavage of LexA, leading to the rapid expression of genes involved in DNA repair, cell cycle arrest, and error-prone translesion synthesis (Bell & Kowalczykowski, 2016, Annual Review of Biochemistry). While the SOS response is a survival mechanism, its error-prone nature is a major driver of genetic diversity and the evolution of antibiotic resistance in bacterial populations. Trp-P-1 specifically induces this pathway by forming DNA adducts that stall replication forks, creating the single-stranded DNA gaps required for RecA activation. In drug discovery, components of the SOS response, particularly RecA, are investigated as therapeutic targets to prevent the emergence of resistance and to potentiate the activity of DNA-damaging antibiotics (Nautiyal et al., 2014, Journal of Medicinal Chemistry). Inhibiting this pathway could theoretically suppress the adaptive mutations that allow pathogens to survive clinical treatment.

Other names

LexA-RecA pathwayDNA damage-inducible (DDI) responseSOS repair systemBacterial SOS response

Inhibition of RecA-mediated LexA cleavage; inhibition of RecA filament formation on single-stranded DNA; blockade of LexA repressor dissociation from operator sites.