The high general stress resistance of the Saccharomyces cerevisiae fil1 adenylate cyclase mutant (Cyr1Lys1682) is only partially dependent on trehalose, Hsp104 and overexpression of Msn2/4-regulated genes.

The initiation of fermentation in the yeast Saccharomyces cerevisiae is associated with a rapid drop in general stress resistance. Previously we identified a mutant which is deficient in fermentation-induced loss of stress resistance (fil1), as a partially inactivating mutant in adenylate cyclase. We have now investigated possible causes of its high stress resistance. Deletion of the TPS1 gene, encoding the first enzyme in the biosynthesis of trehalose, or the heat shock protein gene HSP104 only resulted in a minor effect on heat stress resistance compared with deletion of these genes in a wild-type background. A strain with a deletion of both genes still showed a higher stress resistance in the fil1 background compared to the corresponding wild-type background. Deletion of the transcription factor genes MSN2 and MSN4, which are required for the expression of STRE-regulated genes, resulted in a dramatic drop in heat resistance in the wild-type background but had much less effect in the fil1 mutant. The fil1 msn2Deltamsn4Delta strain remained more heat-resistant than a wild-type strain. A strain in which all four genes, TPS1, HSP104, MSN2 and MSN4, are deleted was very sensitive to heat stress and also to oxidative and salt stress. Presence of the fil1 mutation in such a strain, however, still clearly enhanced heat, oxidative and salt stress resistance. These results indicate that, in addition to trehalose, Hsp104 and the Msn2/4-controlled genes, other factors exist in S. cerevisiae that can, significantly and independently of the known factors, enhance general stress resistance. The mutants described in this work provide a tool to identify these novel components.