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Chromosomal DNA is exposed to continuous damage and repair. Cells contain a number of proteins and specific DNA repair systems that help maintain its correct structure. The SOS response was the first DNA repair system described in Escherichia coli induced upon treatment of bacteria with DNA damaging agents arrest DNA replication and cell division. Induction of the SOS response involves more than forty independent SOS genes, most of which encode proteins engaged in protection, repair, replication, mutagenesis and metabolism of DNA.
Under normal growth conditions the SOS genes are expressed at a basal level, which increases distinctly upon induction of the SOS response.
The recA and lexA genes were the first to be recognized as being involved in SOS induction. Mutations in these genes make cells highly sensitive to UV irradiation. The 27 kDa LexA and the 36 kDa RecA proteins were previously known as recombination proteins operating in the sexual life and genetic exchange of bacteria. Presently, it is known that RecA protein also participates in genetic DNA exchange, in recF, recO, recR, recN and ruvABC-dependent recombinational DNA repair, and, together with LexA protein, plays a major role in the regulation of the SOS response. The down- and up-regulation of the SOS-induced genes is basically an interplay of two proteins, LexA repressor and RecA* where LexA is a transcriptional repressor protein, and RecA* is a coprotease aiding the autocatalytic selfcleavage of LexA.
Agents capable of inducing the SOS response system are, e.g., UV-radiation, MC, methyl methane sulfonate (MMS), and many other chemicals that disrupt DNA, arrest DNA synthesis, and cell division, and lead to accumulation of single stranded (ss) DNA. The level of RecA protein in bacterial cells (like that of UvrD helicase II) is very high. The RecA protein has a strong tendency to form nucleoprotein filaments on ssDNA, and a much weaker one with broken, double stranded (ds) DNA. This probably protects DNA against destruction, and is required for every aspect of RecA activity. The assembly of RecA on ssDNA proceeds in the 5'-3' direction at a ratio of 1 molecule RecA per 3 DNA bases, and requires dATP or ATP, but no ATP-ase activity. The disassembly, in contrast, requires hydrolysis of ATP to ADP and proceeds much more slowly than the assembly. RecA assembled on ssDNA acquires a coprotease activity, RecA*, which facilitates the self-cleavage of LexA protein resulting in derepression of SOS-regulated genes. LexA protein has a weak auto-cleavage activity, but its cleavage and derepression of the SOS genes occur only in the presence of the RecA* coprotease.
Each of the SOS-induced damage-inducible (din) or sos genes has near its promoter/operator site a specific 20-nucleotide-long “SOS-box" (also named, LexA-box) to which the LexA repressor protein is bound, preventing RNA polymerase binding and gene expression. The SOS box has a palindromic structure suggesting that the LexA repressor binds as a dimer, as was later confirmed. The role of the RecA* coprotease in SOS-induced cells therefore is: (i) to assist in the cleavage of LexA protein (202 amino acids) at the Ala84-Gly85 site, which causes derepression of SOS-genes (ii to cleave the CI repressor of λ lambda phage, which transforms the phage from a lysogenic to a lytic form; (iii) to process UmuD → UmuD' by nicking UmuD at the Cys24-Gly25 site which is a prerequisite for the assembly of the SOS-induced mutagenic DNA polymerase V (Pol V) consisting of UmuD'2C. The rate limiting step of Pol V synthesis is UmuD→ UmuD' processing, which occurs much more slowly than the self-cleavage of LexA. The role of Pol V in mutagenesis is translesion synthesis (TLS) across the damage in template DNA, enabling DNA replication, frequently at the cost of fidelity leading to mutation. All these proteins, the CI repressor of λ phage and LexA repressor, UmuD, PolB/DinA (Pol II) and DinB (Pol IV) proteins are homologous within their carboxy-terminal domains, and all are encoded by din (sos) genes regulated under SOS response.
Induction of the SOS response proceeds until 45-60 min after treatment of bacteria with SOS inducing agents and then abruptly ceases. Within this time most of the lesions have been repaired. The timing of the derepression of individual din genes depends on the strength of the LexA repressor binding with the SOS box and on the ease with the LexA repressor is detached from a particular SOS-box.
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