Second-site suppressors

N. (1998) Identification of the mouse neuromuscular degeneration gene and mapping of a second site suppressor allele. Neuron 21, 1327-1337. 

One mechanism that may be important in determining protein plasticity is the occurrence of second site suppressor mutations that serve to compensate for deleterious amino acid substitutions that interfere with... 

The results of genetic analyses also indicate that Sid protein interacts only with the P2 coat protein. P2 mutants resistant to the effects of the Sid protein, mutants sid responsiveness) have been isolated only in gene N (Six etal, 1991). The affected amino acids are clustered and may delineate a critical gpN-Sid contact site. Alternatively, they may identify a hinge region needed to form a more constrained protein fold found only in the smaller capsid. In an effort to distinguish between these two hypotheses, extragenic second-site suppressors of Vrmutations were isolated (Kim et al,... 

D.J. Templeton, K.M. Shokat, A second-site suppressor strategy for chemical genetic analysis of diverse protein kinases, Nat. Methods 2005, 2(6), 435-41. 

Mohr I, Sternberg D, Ward S, Leib D, Mulvey M, Gluzman Y (2001) A herpes simplex virus type 1 gamma34.5 second-site suppressor mutant that exhibits enhanced growth in cultured glioblastoma cells is severely attenuated in animals. J Virol 75 5189-5196 Mossman KL, Saffran HA, Smiley JR (2000) Herpes simplex virus ICPO mutants are hypersensitive to interferon. J Virol 74 2052-2056... 

Lethal or ts mutations under nonpermissive conditions often generate revert-ants. Revertants arise from point mutations and insertions, but not from deletions. Reversion in point mutations may involve the reversal of the original mutation true reversion) or a compensatory mutation elsewhere in the gene (second-site or more generally suppressor mutation). The reversion from insertional mutations usually occurs by appropriate deletion of the inserted part. The suppression restores a wild- or pseudo-wild-type phenotype to a mutant organism in which the primary mutation is still maintained. 

Gros Yes, and then you can have a variety of predisposing mutations that will facilitate this. You could have a variety of primary hits that are inherited and then the retrovirus provides the second hit when it starts repheating in that population. This can reveal oncogenes in different places. Neil Copeland has used BXH2 to identify a great number of retroviral insertion sites that inactivate tumour suppressors or activate oncogenes in clonal tumours observed in these mice (Li et al 1999). 

Schoenfeld A, Davidowitz EJ, Burk RD. A second major native von Hippel-Lindau gene product, initiated fi om an internal translation start site, functions as a tumor suppressor. Proc Natl Acad Sci USA 1998 95 8817-8822. 

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