LYS80P OF SACCHAROMYCES-CEREVISIAE, PREVIOUSLY PROPOSED AS A SPECIFICREPRESSOR OF LYS GENES, IS A PLEIOTROPIC REGULATORY FACTOR IDENTICAL TO MKS1P

In Saccharomyces cerevisiae, an intermediate of the lysine pathway, al pha-aminoadipate semialdehyde (alpha AASA), acts as a coinducer for th e transcriptional activation of LYS genes by Lys14p. The limitation of the production of this intermediate through feedback inhibition of th e first step of the pathway results in apparent repression by lysine. Previously, the lys80 mutations, reducing the lysine repression and in creasing the production of lysine, were interpreted as impairing a rep ressor of LYS genes expression. In order to understand the role of Lys 80p in the control of the lysine pathway, we have analysed the effects of mutations epistatic to lys80 mutations. The effects of lys80 mutat ions on LYS genes expression were dependent on the integrity of the ac tivation system (Lys14p and alpha AASA). The increased production of l ysine in lys80 mutants appeared to result from an improvement of the m etabolic flux through the pathway and was correlated to an increase of the a-ketoglutarate pool and of the level of several enzymes of the t ricarboxylic acid cycle. The LYS80 genes has been cloned and sequenced ; it turned out to be identical to gene MKS1 cloned as a gene encoding a negative regulator of the RAS-cAMP pathway. We conclude that Lys80p is a pleiotropic regulatory factor rather than a specific repressor o f LYS genes. (C) 1997 John Wiley & Sons, Ltd.