Synthetic rescue

Synthetic rescue (or synthetic recovery or synthetic viability when a lethal phenotype is rescued[1]) refers to a genetic interaction in which a cell that is nonviable or sensitive to a specific drug due to the presence of a genetic mutation becomes viable when the original mutation is combined with a second mutation in a different gene.[2] The second mutation can either be a loss-of-function mutation (equivalent to a knockout) or a gain-of-function mutation.[1][3]

Synthetic rescue could potentially be exploited for gene therapy, but it also provides information on the function of the genes involved in the interaction

Types of genetic suppression

Dosage-mediated suppression

Dosage-mediated suppression occurs when the suppression of the mutant phenotype is mediated by the over expression of a second suppressor gene. This can occur when the initial mutations destabilise a protein-protein interaction and over expression of the interacting protein bypass the negative effect of the initial mutation.

Interaction-mediated suppression

Interaction-mediated suppression occurs when a deleterious mutation in a component of a protein complex destabilise the complex. A compensatory mutation in another component of the protein complex can then suppress the deleterious phenotype by re-establishing the interaction between the two proteins. It usually means that the deleterious mutation and the suppressive mutation occurs in two residues that are closely located in the tridimensional structure of the multi-protein complex. As thus this kind of suppression provides indirect information on the molecular structure of the proteins involved.

See also

References

  1. 1 2 Puddu, F.; Oelschlaegel, T; Guerini, I; Geisler, NJ; Niu, H; Herzog, M; Salguero, I; Ochoa-Montaño, B; Viré, E; Sung, P; Adams, DJ; Keane, TM; Jackson, SP (2015). "Synthetic viability genomic screening defines Sae2 function in DNA repair". EMBO Journal 34 (11): 1509–1522. doi:10.15252/embj.201590973. PMID 25899817.
  2. ↑ Motter A. E., Gulbahce N., Almaas E. and Barabasi A.-L., Predicting synthetic rescues in metabolic networks, Molecular Systems Biology 4, 168 (2008).
  3. ↑ Nishikawa T., Gulbahce N., and Motter A. E., Spontaneous reaction silencing in metabolic optimization, PLoS Computational Biology 4, e1000236 (2008).
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