Synthetic rescue

Synthetic rescue (or synthetic recovery or synthetic viability when a lethal phenotype is rescued) refers to a genetic interaction in which a cell that is nonviable, sensitive to a specific drug, or otherwise impaired due to the presence of a genetic mutation becomes viable when the original mutation is combined with a second mutation in a different gene. The second mutation can either be a loss-of-function mutation (equivalent to a knockout) or a gain-of-function mutation.

The term synthetic rescue is derived from synthetic lethality, where the combination of two mutations leads to cell death (whereas neither alone is lethal). Synthetic rescue is the inverse process: instead of causing lethality, the second genetic change rescues the organism from the harmful effects of the first.

This phenomenon occurs in the yeast Saccharomyces cerevisiae, wherein a deletion of the DNA helicase gene SRS2 compensates for the lethality and DNA repair defects caused by the loss of the RAD54 gene.

Synthetic rescue provides insight into the function of the genes involved in intragenic interactions. Synthetic rescue could also potentially be exploited for gene therapy.