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 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 be a loss-of-function mutation (equivalent to a knockout) or a gain-of-function mutation. [1] [3]

Synthetic Reservoir 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 gene suppressor. This can occur when the initial mutations destabilize the protein-protein interaction and the 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 destabilizes 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 dimensions that are closely located in the three-dimensional structure of the multi-protein complex. Thus, this type of suppression provides indirect information on the molecular structure of the proteins involved.

Pathway bypass suppression

tRNA-mediated suppression

Genetic suppression can be mediated by tRNA genes when mutating their anticodon sequence. For example, a tRNA designated for the recognition of the TCA codon and the corresponding insertion of serine in the growing polypeptide chain can mutate so that it recognizes a TAA stop codon and promotes the insertion of serine instead of the termination of the polypeptide chain. This invention may be useful when a mutated mutation (TCA> TAA) prevents the expression of a gene expression or a partial transformation of the polypeptide or degradation of the mRNA by nonsense-mediated decay . The redundancy of tRNA genes makes sure that such mutation would not prevent the normal insertion of serines when the TCA codon specified them.

See also

  • Synthetic lethality
  • Gene therapy
  • Complex networks
  • Suppressor mutation


  1. ^ Jump up to:b 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). “Sae2 function in DNA repair” . EMBO Journal . 34 (11): 1509-1522. doi : 10.15252 / embj.201590973 . PMC  4474527  . PMID  25899817 .
  2. Jump up^ Motter AE Gulbahce N., E. and Almaas Barabasi A.-L.,Predicting synthetic rescues in metabolic networks, Molecular Systems Biology 4, 168 (2008).
  3. Jump up^ Nishikawa T., Gulbahce N., and Motter AE,Spontaneous reaction silencing in metabolic optimization, PLoS Computational Biology 4, e1000236 (2008).

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