Desmoucelles C~Daignan-Fornier B, 2002

Pubmed ID 12016207
Title Screening the yeast "disruptome" for mutants affecting resistance to the immunosuppressive drug, mycophenolic acid.
Authors Christine Desmoucelles, Benoit Pinson, Christelle Saint-Marc, Bertrand Daignan-Fornier
Abstract The immunosuppressive drug mycophenolic acid (MPA) is a potent and specific inhibitor of IMP dehydrogenase, the first committed step of GMP synthesis. A screen for yeast genes affecting MPA sensitivity, when overexpressed, allowed us to identify two genes, IMD2 and TPO1, encoding a homologue of IMP dehydrogenase and a vacuolar pump, respectively. In parallel, 4787 yeast strains, each carrying an identified knock-out mutation, were tested for growth in the presence of MPA, allowing identification of 100 new genes affecting MPA resistance when disrupted. Disturbance of several cellular processes, such as ergosterol biosynthesis, vacuole biogenesis, or glycosylation impaired the natural capacity of yeast to resist MPA, although most of the highly sensitive mutants affected the transcription machinery (19 mutants). Expression of TPO1 and/or IMD2 was strongly affected in 16 such transcription mutants suggesting that low expression of these genes could contribute to MPA sensitivity. Interestingly, the spt3, spt8, and spt20 mutants behaved differently than other Spt-Ada-Gcn5-acetyltransferase (SAGA) mutants. Indeed, in these three mutants, as in previously characterized transcription elongation mutants, IMD2 expression was only affected in the presence of MPA, thus suggesting a possible role for some SAGA subunits in transcription elongation.
Citation J. Biol. Chem. 2002; 277:27036-44


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Papers Phenotype Conditions Collection Tested mutants Data Details
Desmoucelles C~Daignan-Fornier B, 2002 growth (undefined) mycophenolic acid [30-100 mg/L] hap alpha 4,775 Discrete

Curation history

Feb. 10, 2014 Tested strains requested.
Feb. 10, 2014 Data waiting for tested.
Feb. 12, 2014 Tested strains loaded.
Feb. 12, 2014 Data loaded.