TABLE 1.
Screening the yeast disruptome identified genes required for optimal growth of S. cerevisiae in the presence of 400 mM citric acid (pH 3.5)a
| Functional category and ORF | Gene | Characteristic or description |
|---|---|---|
| Metabolism | ||
| Lipid, fatty acid, and isoprenoid metabolism | ||
| YER019W | ISC1 | Weakly similar to human and mouse neutral sphingomyelinase |
| YMR207c | HFA1 | Strongly similar to acetyl coenzyme A carboxylase |
| YMR202w | ERG2 | C8 sterol isomerase |
| YLR056w | ERG3 | C5 sterol desaturase |
| YGL012w | ERG4 | Sterol C24 reductase |
| Carbohydrate metabolism | ||
| YGL156w | AMS1 | α-Mannosidase |
| YLR377c | FBP1 | Fructose-1,6-bisphosphatase |
| YBR126C | TPS1 | α,α-Trehalose-phosphate synthase |
| Nucleotide metabolism | ||
| YMR300c | ADE4 | Amidophosphoribosyltransferase |
| Amino acid metabolism | ||
| YGL154c | LYS5 | l-Aminoadipate-semialdehyde dehydrogenase, small subunit |
| YEL046c | GLY1 | l-Threonine aldolase, low-specific |
| YGL148w | ARO2 | Chorismate synthase |
| YHR025w | THR1 | Homoserine kinase |
| YCR053w | THR4 | Threonine synthase (o-p-homoserine p-lyase) |
| Metabolism of energy reserves | ||
| YBL058w | SHP1 | Potential regulatory subunit for Glc7p |
| Energy generation activities | ||
| YOL079w | Similar to NADH dehydrogenases | |
| Regulation of interaction with cellular environment | ||
| Ion homeostasis | ||
| YGR217W | CCH1 | Calcium channel protein |
| YHR060w | VMA22 | Vacuolar ATPase assembly protein |
| YGR020c | VMA7 | H+-ATPase V1 domain 14-kDa subunit, vacuolar |
| YBR127C | VMA2 | H+-ATPase V1 domain 60-kDa subunit, vacuolar |
| YKL080w | VMA5 | H+-ATPase V1 domain 42-kDa subunit, vacuolar |
| YEL051w | VMA8 | H+-ATPase V1 domain 32-kDa subunit, vacuolar |
| YEL027w | CUP5 | H+-ATPase V0 domain 17-kDa subunit, vacuolar |
| YAL026c | DRS2 | P-type amino-phospholipid-ATPase |
| YLR447c | VMA6 | H+-ATPase V0 domain 36-kDa subunit, vacuolar |
| YDL185w | TFP1 | H+-ATPase V1 domain 69-kDa catalytic subunit, vacuolar |
| YHR026w | PPA1 | H+-ATPase 23-kDa subunit, vacuolar |
| Cellular transport and transport mechanisms | ||
| YDR320c | SWA2 | Clathrin-binding protein required for normal clathrin function |
| Control cellular organization | ||
| Cell wall | ||
| YCL007c | CWH36 | Affects the mannoprotein layer of the cell wall |
| YLR390w-a | CCW14 | Secretory stress response protein 1 |
| YGR036c | CAX4 | Required for full levels of dolichol-linked oligosaccharides in the endoplasmic reticulum |
| YJL095W | BCK1 | Cell wall integrity pathway, nutrient sensing, and growth control |
| YDR323c | PEP7 | Vacuolar segregation protein |
| YJR059W | PTK2 | Involved in polyamine uptake |
| Cell fate | ||
| YNL084c | END3 | Required for endocytosis and cytoskeletal organization |
| YGR167w | CLC1 | Clathrin light chain |
| YDR388w | RVS167 | Reduced viability upon starvation protein |
| YAL016w | TPD3 | Ser/Thr protein phosphatase 2A, regulatory chain A |
| YDR099W | BMH2 | Suppressor of clathrin deficiency |
| Transcription | ||
| YBR112c | CYC8 | General repressor of transcription |
| YPL129w | ANC1 | TFIIF subunit (transcription initiation factor), 30 kDa |
| YOR295w | UAF30 | Subunit of RNA polymerase I transcription factor |
| YOR290c | SNF2 | Component of SWI/SNF global transcription activator complex |
| YMR228w | MTF1 | RNA polymerase-specific factor, mitochondrial |
| YKL062w | MSN4 | Transcriptional activator |
| YGL071W | RCS1 | Activates transcription in response to iron deprivation |
| Protein synthesis | ||
| YBR191w | RPL21A | Ribosomal protein L21.e |
| YNL073w | MSK1 | Lysyl-tRNA synthetase, mitochondrial |
| YOL023w | IFM1 | Translation initiation factor 2, mitochondrial |
| Cellular communication/signal transduction pathway | ||
| YMR016c | SOK2 | Regulatory protein in the protein kinase A signal Transduction pathway |
| YLR113w | HOG1 | Ser/Thr protein kinase of MAPK family |
| YLR006c | SSK1 | Two-component signal transducer |
| Protein fate | ||
| YLR148w | PEP3 | Vacuolar membrane protein |
| YPL045w | VPS16 | Vacuolar sorting protein |
| YLR396c | VPS33 | Vacuolar sorting protein |
| YCR069w | SCC3 | Peptidyl-prolyl cis-trans isomerase precursor |
| YML078w | CPR3 | Cyclophilin (peptidylprolyl isomerase) |
| YMR150C | IMP1 | Protease, mitochondrial |
| Cell rescue, defense, and virulence | ||
| Detoxification | ||
| YJR104c | SOD1 | Copper-zinc superoxide dismutase |
| Cell cycle and DNA processing | ||
| YIL153w | RRD1 | Similar to human and rabbit phosphotyrosyl phosphatase activators and YPL152w |
| YGR188c | BUB1 | Ser/Thr protein kinase |
| YIL035c | CKA1 | Casein kinase II, catalytic alpha chain |
| YPL239W | YAR1 | Ankyrin repeat-containing protein |
| YJR144w | MGM101 | Mitochondrial genome maintenance protein |
| Unknown function | ||
| YMR216c | SKY1 | Similar to Schizosaccharomyces pombe dsk1, human SRPK1, and other protein kinases |
| YDL204W | Similar to hypothetical protein YDR233c | |
| YLR326w | ||
| YOR331c | Questionable ORF | |
| YLR334c | Questionable ORF | |
| YOR161C | Similarity to Caenorhabditis elegans cosmid F35C8 | |
| YKL169c | ||
| YBR101c | Weakly similar to S. pombe hypothetical protein SPBC3B9.01 | |
| YLR346c | Weakly similar to YGR035c | |
| YHR198c | ||
| YKL102c | ||
| YEL045c | Weakly similar to cytochrome c oxidase III of Trypanosoma brucei kinetoplast | |
| YLR047c | Similar to hypothetical protein YGL160w | |
| YPL144w | Hypothetical protein |
a
Ten of the 69 citric acid-sensitive gene deletions were of particular interest, because the genes encode known regulatory proteins that could be involved in signalling an adaptive response to citric acid stress. The 10 genes are shown in bold type.