The contribution of the non‐homologous region of Prs1 to the maintenance of cell wall integrity and cell viability

Abstract The gene products of the five‐membered PRS gene family in S. cerevisiae have been shown to exist as three minimal functional entities, Prs1/Prs3, Prs2/Prs5 and Prs4/Prs5, each capable of supporting cell viability. The Prs1/Prs3 heterodimer can be regarded as the most important since its loss causes temperature sensitivity. It has been shown that the GFP signal generated by an integrated GFP‐Prs1 construct is lost in the absence of Prs3. In addition to interacting with Prs3, Prs1 also interacts with Slt2, the MAPK of the cell wall integrity (CWI) pathway. Lack of the non‐homologous region (NHR1‐1) located centrally in Prs1 abolished the temperature‐induced increase in Rlm1 expression. Furthermore, in vitro point mutations generated in PRS1 corresponding to missense mutations associated with human neuropathies or in the divalent cation and/or PRPP binding sites also display increased Rlm1 expression at 30°C and 37°C and most give rise to caffeine sensitivity. Human PRPS1 cDNA cannot rescue the synthetic lethality of a prs1Δ prs5Δ strain since it lacks sequences corresponding to NHR1‐1 of yeast Prs1. 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 a prs1Δ prs5Δ strain implying that impaired CWI may contribute to the observed loss of viability. © 2013 Federation of European Microbiological Societies. Published by Blac...
Source: FEMS Yeast Research - Category: Research Authors: Tags: Research Paper Source Type: research