After 30 Years of Study, the Bacterial SOS Response Still Surprises Us

1174 I n order to survive in various environmental conditions, cells have a repertoire of genes that they can choose to express or silence according to their needs. Among this vast collection of genetically controlled networks, the SOS response is an inducible DNA repair system that allows bacteria to survive sudden increases in DNA damage. The importance of the SOS response is underscored by the observation that this regulatory network is widely present in bacteria, reflecting the need for all living cells to maintain the integrity of their genome. The first experimental support for the existence of an inducible DNA repair network in Escherichia coli was found 30 years ago by Miroslav Radman, who introduced the term " SOS response " to describe this network [1]. Two proteins play key roles in the regulation of the SOS response: a repressor named LexA and an inducer, the RecA filament. During normal growth, the LexA repressor binds to a specific sequence—the SOS box, present in the promoter region of SOS genes—and prevents their expression. SOS genes are repressed to different degrees under normal growth conditions. This depends on the exact sequence of their SOS box (the region of a promoter that is recognized by LexA), its position in the promoter region, and the strength of the promoter. When the cell senses the presence of an increased level of DNA damage, the LexA repressor undergoes a self-cleavage reaction and the SOS genes are de-repressed (Figure 1). A nucleoprotein complex—the RecA filament— induces the LexA cleavage reaction. RecA is a ubiquitous protein, present in nearly all bacteria and conserved in all organisms, including humans. It specifically binds single-stranded DNA (ssDNA), forming a nucleoprotein filament that has two functions [2]: the RecA filament may either invade a homologous double-stranded DNA sequence and catalyze strand exchange (the key reaction of homologous recombination), or it may promote LexA cleavage (thereby inducing the SOS response). However, RecA binding to ssDNA is also regulated. It is prevented in vivo by the ubiquitous presence of the ssDNA binding protein. Two systems allow RecA to overcome the ssDNA binding protein barrier on certain substrates: the RecFOR proteins assist RecA binding to single-strand gaps, and the RecBC proteins directly load RecA on the processed double-strand ends. Consequently, DNA-damaging agents that induce the formation of DNA single-strand gaps, such as UV light, will induce the SOS response only if the RecFOR proteins are …