The SOS system: A complex and tightly regulated response to DNA damage

Abstract

Genomes of all living organisms are constantly threatened by endogenous and exogenous agents that challenge the chemical integrity of DNA. Most bacteria have evolved a coordinated response to DNA damage. In Escherichia coli, this inducible system is termed the SOS response. The SOS global regulatory network consists of multiple factors promoting the integrity of DNA as well as error-prone factors allowing for survival and continuous replication upon extensive DNA damage at the cost of elevated mutagenesis. Due to its mutagenic potential, the SOS response is subject to elaborate regulatory control involving not only transcriptional derepression, but also post-translational activation, and inhibition. This review summarizes current knowledge about the molecular mechanism of the SOS response induction and progression and its consequences for genome stability. Environ. Mol. Mutagen. 60:368-384, 2019. © 2018 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

Keywords: Escherichia coli; LexA regulon; RecA; SOS response; TLS; mutator effect.

Figure 1

Schematic representation of the SOS induction process in E. coli. During normal growth, the LexA repressor binds to the operator sequence in the promoter region of SOS genes, preventing their expression. Upon DNA damage, ssDNA accumulates when a replication fork stalls during replication of DNA containing lesions. RecA binds the ssDNA, and in the presence of (d)ATP converts to an activated form (nucleoprotein filament RecA*). RecA* stimulates self‐cleavage of LexA, leading to derepression of SOS genes. After the damage has been addressed, elimination of the inducing signal allows LexA to reaccumulate and repress the SOS genes.

Figure 2

Comparison of two DNA polymerase structures. (A) low fidelity E. coli DNA Pol IV and (B) high fidelity Thermus aquaticus DNA polymerase I (Klentaq1). Encircled are polymerase catalytic active sites. The polymerase domains are labeled in red (palm), blue (finger), green (thumb), gray (N‐terminal domain of Klentaq1), purple (little finger domain, unique for Y‐family polymerases). The images were generated using PyMol (DeLano, 2002) based on the crystal structure of DNA Pol IV from E. coli in complex with DNA (PDB ID code 5YYD) and the ternary complex structure of the large fragment of Thermus aquaticus DNA polymerase I (PDB ID code 3KTQ).