Use of genetically engineered microorganisms (GEMs) for pollution abatement has been limited because of the risks associated with their uncontrolled release in environment. In this study, a pollutant-dependent bacterial containment system was constructed in E. coli JM109. The system consisted of two plasmids containing a killing element and a regulatory element respectively. The survival of strains can be regulated by the concentration of salicylate in environment. In the presence of salicylate, the expression of the suicide gene gef was inhibited with the synthesis of LacI protein, leading to the normal proliferation of the strain. While in the absence of salicylate, the expression of the regulatory element was cancelled, and the expression of the suicide gene gefled to a high rate of cell killing. This containment system can be used as a model during the construction of genetically engineered strains for bioremediation.
Biodegradation, Environmental ; Containment of Biohazards ; methods ; Environmental Pollutants ; metabolism ; Escherichia coli ; genetics ; metabolism ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Genes, Lethal ; genetics ; Genetic Engineering ; methods ; Organisms, Genetically Modified ; genetics ; metabolism ; Salicylates ; pharmacology

Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particular homologous recombination (HR), are highly sensitive to DNA-damaging agents. Thus, HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; genetics ; DNA Repair ; drug effects ; genetics ; Gene Expression Regulation, Neoplastic ; drug effects ; Genes, Lethal ; genetics ; Genes, Tumor Suppressor ; drug effects ; Genes, cdc ; drug effects ; Humans ; Mutagenesis ; Poly(ADP-ribose) Polymerase Inhibitors ; Rad52 DNA Repair and Recombination Protein ; antagonists & inhibitors ; Recombination, Genetic ; drug effects ; genetics