SOS Response PDF

## The SOS Response While most DNA repair mechanisms are constitutive (i.e., active all the time), a few are activated in response to some signal, such as a blocked replication fork. Most notable is the SOS response system, characterized in *E. coli* as a complex regulatory scheme in which the prod...

## The SOS Response While most DNA repair mechanisms are constitutive (i.e., active all the time), a few are activated in response to some signal, such as a blocked replication fork. Most notable is the SOS response system, characterized in *E. coli* as a complex regulatory scheme in which the products of two genes, *recA* and *lexA*, govern the expression of a number of other genes involved in DNA repair (Figure 10-9). Some of these genes (*uvrA* and *uvrB*) are involved in excision repair, while others like *umuC* and *umuD* are required to help replication bypass the offending lesion. In order to continue DNA replication across a region containing a thymine dimer, the editing function of polymerase III must be relaxed, otherwise the helical distortion caused by the dimer would trigger pol III's 3' → 5' proofreading activity, and the replication fork would become stalled. Relaxation of proofreading is not without its own inherent hazards. It leads to error-prone DNA replication, and results in a higher-than-normal level of mutagenesis. Because this is detrimental to the cell, expression of the genes involved in the SOS response must be carefully regulated in order to maintain the fidelity of DNA replication under normal circumstances. In the presence of certain types of potentially lethal DNA damage, the system is switched "on" as a last-ditch effort to allow the cell to survive (hence the name "SOS" response). The enhanced mutagenesis that results may be seen as a benefit in that it may result in progeny that, through mutation, are better adapted to live in the noxious environment that led to the induction of the SOS system. The genes of the SOS response are ordinarily maintained in an "off" state. This is accomplished by the *lexA* gene product, the LexA repressor, which binds to an operator sequence near each gene and prevents its transcription. The LexA repressor even represses its own expression, so that only small amounts of this protein are synthesized routinely. (Regulation of gene expression in prokaryotes will be discussed in greater detail in Chapter 11.) The RecA protein plays two different, complementary roles in the SOS response. First, it inhibits the editing function of DNA polymerase III. It binds to the distorted region of the DNA molecule containing the dimer; when pol III encounters this region, the RecA protein interacts with the polymerase subunit involved in proofreading. This results in inhibition of pol III's editing function and allows the replication to proceed. Binding of the RecA protein to the single-stranded DNA also has a second effect: it causes a conformational change in the RecA protein (→ RecA*). This activated form of the RecA* protein interacts with the LexA repressor protein, stimulating the LexA repressor to inactivate itself by proteolytic cleavage. With the repressor inactivated, all of the genes involved in the SOS response can be expressed, and the enzymes required for DNA repair are synthesized. (Although this also leads to high levels of expression of the *lexA* gene, the repressor will continue to be cleaved as long as the activated RecA* is present.) Eventually, DNA repair will be completed and the RecA protein will once again lose its proteolytic activity. This will allow LexA repressor levels to increase, shutting off the expression of the genes involved in the SOS response, and allowing pol III to resume normal proofreading. ### The SOS Response - Figure 10-9 **The SOS Response, in uninduced cells, the LexA protein [O] is not activated and, thus, does not facilitate self-proteolysis of the LexA protein [□]. The LexA protein functions as a repressor, turning off transcription of many different genes, including the *recA* gene and the *lexA* gene itself (i.e., it is autoregulatory). DNA-damaging agents induce the SOS response by activating RecA protein to RecA*[●], which facilitates the self-cleavage of LexA protein [N] and several other proteins, including the repressor. After LexA protein is cleaved, it cannot function as a repressor, resulting in transcription of all of the genes regulated by the LexA protein. As the SOS genes repair the DNA damage, RecA* returns to RecA, LexA is no longer cleaved, and accumulation of LexA represses the SOS genes. ** | **SOS Repressed** | **SOS Induced** | | -------------------------- | -------------------------- | | DNA damage (1) | DNA damage repaired (1) | | RecA converted to RecA* (2) | RecA returns to RecA (2) | | RecA facilitates LexA self-cleavage (3) | LexA no longer self-cleaved (3) | | Increased synthesis of SOS proteins (4) | LexA represses SOS genes (4) | | Error prone repair induced (5) | LexA represses *lexA* (5) | ## Summary This document describes the SOS response, a system in *E. coli* that is activated in response to DNA damage. The SOS response is characterized by the activation of *recA* and *lexA* genes, which leads to the expression of a number of other genes involved in DNA repair. The SOS response is carefully regulated to ensure the fidelity of DNA replication.