The contribution of the nonhomologous region of P rs1 to the maintenance of cell wall integrity and cell viability

The gene products of the five‐membered PRS gene family in S accharomyces cerevisiae have been shown to exist as three minimal functional entities, P rs1/ P rs3, P rs2/ P rs5, and P rs4/ P rs5, each capable of supporting cell viability. The P rs1/ P rs3 heterodimer can be regarded as the most important because its loss causes temperature sensitivity. It has been shown that the GFP signal generated by an integrated GFP ‐ P rs1 construct is lost in the absence of P rs3. In addition to interacting with P rs3, P rs1 also interacts with S lt2, the MAPK of the cell wall integrity ( CWI ) pathway. Lack of the nonhomologous region ( NHR 1‐1) located centrally in Prs1 abolished the temperature‐induced increase in R lm1 expression. Furthermore, in vitro point mutations generated in PRS1 corresponding to missense mutations associated with human neuropathies or in the divalent cation and/or 5‐phosphoribosyl‐1(α)‐pyrophosphate binding sites also display increased R lm1 expression at 30 °C and 37 °C and most give rise to caffeine sensitivity. Human PRPS 1 c DNA cannot rescue the synthetic lethality of a prs1Δ prs5Δ strain because it lacks sequences corresponding to NHR 1‐1 of yeast P rs1. The correlation between caffeine sensitivity and increased basal expression of Rlm1 in the altered versions of PRS1 can be extended to their inability to rescue the synthetic lethality of a prs1Δ prs5Δ strain implying that impaired CWI may contribute to the observed loss of viability.