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The magical mechanism of gene repair: How does RecA protein trigger the SOS response?
The SOS response is a global response mechanism when cells face DNA damage. During this process, the cell cycle is paused and the DNA repair and gene mutation processes are initiated. The core of this phenomenon lies in the RecA protein. When single-stranded DNA appears, the RecA protein is stimulated and begins a series of biochemical reactions, which in turn initiates the SOS response.
"The role of RecA protein is not only to repair DNA, but also a new perspective on how cells respond to stress."
Discovery of the SOS response
The concept of SOS response was first proposed by Evelyn Witkin. By studying the phenotypic characteristics of mutant E. coli, Witkin and his postdoctoral fellow Miroslav Radman detailed the bacteria's SOS response to UV radiation. The discovery of this system not only proves that cells can coordinate their response to DNA damage, but also opens up in-depth research on cellular stress responses.
Mechanisms of the SOS response
Under normal growth conditions, the SOS gene is negatively regulated by the LexA inhibitory protein dimer. LexA represses the expression of these genes by binding to a specific 20-bp consensus sequence (SOS box). However, when DNA is damaged, as single-stranded DNA regions accumulate at the replication fork, the RecA protein begins to form filamentous structures around these single-stranded DNA regions in an ATP-dependent manner and becomes activated.
"Activation of the RecA protein causes the LexA inhibitory protein to self-cleave, thereby releasing the inhibition of the SOS gene."
When the concentration of LexA decreases, the corresponding SOS gene begins to be expressed. This process is gradual and orderly. LexA has a weaker affinity for certain operators (such as lexA, recA, uvrA, etc.), so these genes are fully activated first in the SOS response and are preferentially expressed during the repair process.
Antibiotic resistance and the SOS response
The study found that the SOS response system may lead to mutations and further cause antibiotic resistance. During the SOS response, the world's three low-fidelity DNA polymerases (Pol II, Pol IV, and Pol V) increase the mutation rate. Therefore, many research teams are now targeting these proteins in the hope of developing drugs that can prevent SOS repair.
"By extending the time it takes pathogens to evolve antibiotic resistance, the long-term effectiveness of some antibiotics could be improved."
Genotoxicity testing
In Escherichia coli, various classes of DNA damaging agents can initiate the SOS response. By fusing the lac operator to an operator controlled by an SOS-associated protein, a simple colorimetric assay can be implemented to detect genotoxicity. When a lactose analog is added, it is degraded by beta-galactosidase to produce a colored compound that can be quantitatively measured by a spectrophotometer. The degree of color change is an indirect measure of the degree of DNA damage.
SOS response of cyanobacteria
Cyanobacteria are the only prokaryotes capable of oxygen-evolving photosynthesis, which has had a significant impact on the Earth's oxygen atmosphere. In some marine cyanobacteria such as Prochlorococcus and Synechococcus, it was found that they have an SOS system similar to that of E. coli, which helps in their DNA repair because they encode genes that are homologous to the E. coli SOS genes (such as lexA and sulA).
With the in-depth study of RecA protein and SOS response mechanism, can scientists find new strategies to prevent pathogens from evolving resistance in the future?
