# Unbridled Integons: A Matter of Host Factors
## 4 Host Factors Influencing the Expression of the Integrase  
### Integrase Expression and SOS Response  
#### 4.1.1 The Integrase Gene Is Part of the SOS Regulon  
The SOS response is an almost ubiquitous response of cells to genotoxic stresses, sensed as the accumulation of single-stranded DNA (ssDNA). The term \"SOS response\" was coined by [PERSON] in the 70's and was originally associated with DNA damage [27] and later with HGT [28]. This pathway involves two main regulators: the LexA and RecA proteins. LexA is a specific transcriptional repressor [29]. The RecA protein acts as a detector of the \"abnormal\" presence of single-stranded ssDNA in the cell, which can come from double-strand break repair or arrested replication forks, as well as from the entry of exogenous DNA molecule by HGT [30]. RecA forms a nucleophilicment with the ss DNA molecule and becomes activated to stimulate the LexA inactivation by autoproteolysis and subsequent degradation by ClpXP and Lon [31]. Inactivation of LexA leads to the derepression of all genes belonging to the SOS regulon. In _Escherichia coli_, this regulon includes 57 genes that code for proteins involved in DNA replication, repair, and recombination; cell division arrest; and translesional replication systems [32]. In _V. cholerae_, the SOS regulon overlaps the _E. coli_ one but also includes several additional genes [33]. In absence of trigger, LexA forms a dimer and acts as a transcriptional repressor for genes belonging to the SOS regulon by binding to a specific operator sequence (the LexA-box) in their promoter region [34], which consists of a CTGT(N)sACAG motif in gamma-proteobacteria [35]. The success of the integrin system resides in the fact that the cassettes it contains can be shuffled until an  
Figure 3: Regulation of the _Vibrio cholerae_ SCI promoters. The _intIA_ and cassette promoters are regulated by several processes. The main triggering signal for integrase expression is the bacterial SOS response. Indeed, the integrase expression is repressed in normal conditions by the binding of the LexA repressor on the P\({}_{\text{int}}\) LexA box. In stress conditions (genotoxic stress) or in conditions of horizontal transfer of single-stranded DNA (ssDNA), the RecA- ss nucleofilament is formed and induces the autoproteolysis of the LexA repressor, and the integrase is expressed. Both integrase (P\({}_{\text{int}}\)) and cassette (P\({}_{\text{C}}\)) promoters are regulated by the catabolic repression since both share a CRP box. For instance, in presence of glucose, the P\({}_{\text{int}}\) and P\({}_{\text{C}}\) promoters do not efficiently function. optimal organization of the array is selected in a given period and environment context. If this is not the case, unneeded shuffling might do more harm than good to the cell. Indeed, as seen for many recombinases, the constitutive expression of the integrase over a long period of time can prove toxic for the cell [36]. This implies that the integrase expression has to be set \"on\" and \"off\", depending on the need of the cell to get access to the diversity of functions encoded in the cassettes. In the case of integrins, like for other MGE [37], this is achieved through the integration of the integrase expression in the SOS response [38], thanks to the presence of a LexA box in the P\({}_{\text{int}}\) promoters of many integrins integrases [39]. The expression of both integrases--the integrase of the SI of _V. cholerae_ (IntIA, Figure 3) and of the class 1 MI (IntI1)--was analyzed. Induction of the SOS response increased the expression of a \(\beta\)-galactosidase reporter of integrase transcription 4.5-fold for IntI1 in _E. coli_ and 37-fold for IntIA in _V. cholerae_[39]. Furthermore, there is a strong correlation between the LexA regulation and the functionality of the integrase: P\({}_{\text{int}}\) lacking lexA box or with a poorly conserved LexA motif is often associated with a truncated, non-functional integrase [39].