Restauration

In molecular biology, restoration refers to a mutation that restores the original phenotype. Restorations are based on a phenotypic, but not genotypic, restoration of the wild-type phenotype. This distinguishes the process of restoration from that of reversion. In restoration, a gene defect is corrected functionally, i.e. phenotypically, by mutations at other positions of the gene (intragenic) or other genes (intergenic). Reversion, on the other hand, restores the original nucleotide sequence.

Whether restoration or reversion is present can usually be determined by crossing the revertant with the wild type: if organisms or strains with the mutant phenotype occur in the progeny, restoration is present; if the progeny show only the wild-type phenotype, this is a true reversion.

Reversion mutations play a significant role, for example, in the development of therapy resistance to chemotherapeutic agents of breast and ovarian carcinomas as well as pancreatic and prostate carcinomas. Tumors in these patients tend to lose both copies of the wild-type BRCA gene, making them particularly sensitive to platinum drugs and poly(ADP-ribose) polymerase inhibitors (PARPi), the therapies of choice in these diseases. Pharmacological inhibition of DNA end-joining repair pathways leads to improved drug treatment outcomes by preventing the acquisition of reversion mutations in BRCA genes, for example (Tobalina L et al. 2021).

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