Genetic Evidence for Interaction between Nonhomologous Proteins in Yeast and a Case of Suppression at the HIS1 Locus.

The HIS1 and THR4 loci are the structural genes for phosphoribosyl-ATP pyrophosphorylase and threonine synthetase, respectively. The allele his1-1S has no enzyme activity at 30 degrees , but does have activity at 15 degrees provided the cell contains the wild-type THR4 allele or a suppressing allele at another locus, designated SUP(his1-1S). Under these conditions, cells with the his1-1S mutation are capable of growth on minimal medium at 15 degrees . Three kinds of reversions of a his1-1S thr4 sup(his1-1S) strain to histidine prototrophy have been obtained: (1) his1-1S locus reversions to HIS1 that restore growth without added histidine at 30 degrees , (2) thr4 reversions to THR4 that simultaneously eliminate the requirement for threonine and restore the low-temperature effect on the his1-1S allele, and (3) mutations from sup to SUP. The SUP allele is not an ochre suppressor, and it is not linked to either HIS1, THR4 or a centromere. It may represent a missense suppressor. It is proposed that the effect of THR4 is caused by aggregation of the wild-type threonine synthetase with defective his1-1S monomers, causing a favorable conformational change in the histidine protein that restores limited enzymatic activity. This can be regarded as a case of complementation between nonhomologous proteins.