Regulation of Gene Expression in Prokaryotes:- Induction of the SOS Response Requires Destruction of Repressor Proteins
Extensive DNA damage in the bacterial chromosome triggers the induction of many distantly located genes. This response, called the SOS response (p. 976), pro vides another good example of coordinated gene regulation. Many of the induced genes are involved in DNA repair . The key regulatory proteins are the RecA protein and the LexA repressor. The LexA repressor (Mr 22,700) inhibits transcription of all the SOS genes (Fig. 1), and induction of the SOS response requires removal of LexA. This is not a simple dissociation from DNA in response to binding of a small molecule, as in the regulation of the lac operon described above. Instead, the LexA repressor is inactivated when it catalyzes its own cleavage at a specific Ala–Gly peptide bond, producing two roughly equal protein fragments. At physiological pH, this autocleavage reaction requires the RecA protein. RecA is not a protease in the classical sense, but its interaction with LexA facilitates the repressor’s self-cleavage reaction. This function of RecA is sometimes called a co-protease activity. The RecA protein provides the functional link between the biological signal (DNA damage) and induction of the SOS genes. Heavy DNA damage leads to numerous single-strand gaps in the DNA, and only RecA that is bound to single-stranded DNA can facilitate cleavage of the LexA repressor (Fig. 1, bottom). Binding of RecA at the gaps eventually activates its co protease activity, leading to cleavage of the LexA re pressor and SOS induction.
During induction of the SOS response in a severely damaged cell, RecA also cleaves and thus inactivates the repressors that otherwise allow propagation of certain viruses in a dormant lysogenic state within the bacterial host. This provides a remarkable illustration of evolutionary adaptation. These repressors, like LexA, also undergo self-cleavage at a specific Ala–Gly peptide bond, so induction of the SOS response permits replication of the virus and lysis of the cell, releasing new viral particles. Thus, the bacteriophage can make a hasty exit from a compromised bacterial host cell.
FIGURE 1 SOS response in E. coli. See Table 25–6 for the functions of many of these proteins. The LexA protein is the repressor in this system, which has an operator site (red) near each gene. Because the recA gene is not entirely repressed by the LexA repressor, the normal cell contains about 1,000 RecA monomers. 1 When DNA is extensively damaged (e.g., by UV light), DNA replication is halted and the number of single-strand gaps in the DNA increases. 2 RecA protein binds to this damaged, single-stranded DNA, activating the protein’s coprotease activity. 3 While bound to DNA, the RecA protein facilitates cleavage and inactivation of the LexA repressor. When the repressor is inactivated, the SOS genes, including recA, are induced; RecA levels increase 50- to 100-fold.
