Profiling The Compendium Of Changes In Saccharomyces cerevisiae Due To Mutations That Alter Availability Of The Main Methyl Donor S-Adenosylmethionine
The SAM1 and SAM2 genes encode for S-AdenosylMethionine (AdoMet) synthetase enzymes, with AdoMet serving as the main cellular methyl donor.  We have previously shown that independent deletion of these genes alters chromosome stability and AdoMet concentrations in opposite ways in Saccharomyces cerevisiae. To characterize other changes occurring in these mutants, we grew wildtype, sam1?/sam1?, and sam2?/sam2? strains in 15 different Phenotypic Microarray plates with different components and measured growth variations. RNA-Sequencing was also carried out on these strains and differential gene expression determined for each mutant. We explored how the phenotypic growth differences are linked to the altered gene expression, and hypothesize mechanisms by which loss of the SAM genes and subsequent AdoMet level changes, impact pathways and processes. We present six stories, discussing changes in sensitivity or resistance to azoles, cisplatin, oxidative stress, arginine biosynthesis perturbations, DNA synthesis inhibitors, and tamoxifen, to demonstrate the power of this novel methodology to broadly profile changes due to gene mutations. The large number of conditions that result in altered growth, as well as the large number of differentially expressed genes with wide-ranging functionality, speaks to the broad array of impacts that altering methyl donor abundance can impart. Our findings demonstrate that some cellular changes are directly related to AdoMet-dependent methyltransferases and AdoMet availability, some are directly linked to the methyl cycle and its role in production of several important cellular components, and others reveal impacts of SAM gene mutations on previously unconnected pathways. Overall design: To explore similarities and differences due to the loss of the paralogous S-adenosylmethionine synthetase genes, SAM1 and SAM2, we deleted each gene indepdendently and explored gene expression and phenotype differences.