Previously, we proposed a test system that allows one to search for genes that influence the properties of Sup35 and Sup45 proteins. This test is based on the phenomenon of the lethality of diploids that combine mutations in the SUP45 gene with [PSI⁺] prion. The lethality of this combination depends on both the type of sup45 mutation and the properties of the prion. The [PSI⁺] variant, which is a strong suppressor ([PSI⁺]^S), causes synthetic lethality with all the nonsense mutations and some missense sup45 mutations in the heterozygote state. The presence of extra copies of the tested gene, which affects the phenotypic manifestation of the prion [PSI⁺] or properties of the termination factors of translation leads to a increase or decrease in diploid lethality. The screening of the gene library using this test system allowed us to establish the effect of ten fragments of genomic DNA of yeast on synthetic lethality. The deletion analysis of these regions has led to the identification of the HLJ1 and TEF2 genes, which affects the prionization of the Sup35 protein and/or the efficiency of translation termination.