Disease relevance of SCT1

• Following ethyl methanesulfonate mutagenesis of top1 delta yeast cells expressing plasmid-borne wild-type DNA topoisomerase I, six dominant suppressors of camptothecin toxicity were isolated that define a single genetic locus, sct1 [1].

High impact information on SCT1

• We find that the G1-specific transcription factor p65cdc10-p72res1/sct1 which controls the expression of S-phase genes is fully activated in pheromone, unlike the analogous control in budding yeast [2].
• Mutant SCT1 cells expressed DNA topoisomerase I protein of similar specific activity and camptothecin sensitivity to that of congenic, drug-sensitive sct1 cells, yet were resistant to camptothecin-mediated lethality [1].
• SCT1 cell sensitivity to other DNA-damaging agents suggests that alterations in SCT1 function suppress camptothecin-induced DNA damage produced in the presence of yeast DNA topoisomerase I [1].
• Moreover, camptothecin-treated SCT1 cells did not exhibit the G2-arrested, terminal phenotype characteristic of drug-treated wild-type cells [1].
• To address why we observed alterations in phospholipid turnover specific to phosphatidylcholine produced through the CDP-choline pathway in gat1 and gat2 yeast we tested their sensitivity to various cytotoxic lysolipids and observed that gat2 cells were more sensitive to lysophosphatidylcholine, but not other lysolipids [3].

Biological context of SCT1

• Disruption of the open reading frame YBL011w, corresponding to a gene previously identified as a choline transporter suppressor (SCT1), resulted in a substantial decrease of total cellular G-3-P acyltransferase activity [4].
• Here we report SCT1 is allelic to PDR1 and that a Thr-879 to Met substitution in the PDR1-101 transcription factor confers multiple drug resistance [5].
• Gene disruption experiments showed that SCT1 is not an essential gene under the standard culture conditions [6].
• Genetic inactivation of either GAT1 or GAT2 did not alter cell growth but inactivation of both resulted in growth cessation [3].
• Molecular characterizations of the genes revealed that a missense mutation in YKR067w accounted for a defect in the activities of the G-3-P acyltransferase in the yeast mutant strain TTA1 [4].

Associations of SCT1 with chemical compounds

• Our data showed that gat1 and gat2 yeast were resistant and sensitive to lysoplatelet activating factor, platelet activating factor, and the anti-tumor lipid edelfosine, respectively, indicating that their sensitivity to these compounds was not because of differences in rates of phosphatidylcholine deacylation [3].
• In each case, the response of the dihydroxyacetone phosphate acyltransferase activity was similar to that of the sn-glycerol-3-phosphate acyltransferase [7].
• GPAT activity was increased 3-fold, while DHAPAT activity was increased up to 9-fold in wild type cells grown in a nonfermentable carbon source compared to that of glucose-grown cells [8].
• The ratio of GPAT/DHAPAT activity was 12 in glucose-grown cells but only 4 in cells grown in glycerol/ethanol [8].
• To understand how phosphatidic acid biosynthesis is controlled in Saccharomyces cerevisiae, we studied the regulation of three enzyme activities involved in the synthesis of this glycerolipid precursor, i.e., glycerophosphate acyltransferase (GPAT), dihydroxyacetone phosphate acyltransferase (DHAPAT), and acyl DHAP reductase [8].

Regulatory relationships of SCT1

• Isolation and characterization of a SCT1 gene which can suppress a choline-transport mutant of Saccharomyces cerevisiae [6].
• SCT1 mutants suppress the camptothecin sensitivity of yeast cells expressing wild-type DNA topoisomerase I [1].

Other interactions of SCT1

• Yeast SCT1 mutants were isolated in a screen for mutations in genes other than TOP1 that result in camptothecin resistance [5].

References