ArticleThe Journal of biological chemistry2003
Functional distinctions between IMP dehydrogenase genes in providing mycophenolate resistance and guanine prototrophy to yeast.
Article in The Journal of biological chemistry, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 81 citations in OpenAlex.
- Structural dynamics of RNA polymerase II throughout the nucleotide addition cycle.Nature communications · 2026Article
- Structural Dynamics of RNA Polymerase II During Nucleotide Addition Cycle.bioRxiv : the preprint server for biology · 2026Article
- In thePNAS nexus · 2026Article
- Important role in transcription start site selection for the RNA polymerase II-TFIIE-TFIIH interface in Saccharomyces cerevisiae.Genetics · 2026Article
- RNA polymerase II-TFIIE-TFIIH interface functions in transcription start site selection inbioRxiv : the preprint server for biology · 2025Article
- A Saccharomyces cerevisiae knockout screen for genes critical for growth under sulfur- and nitrogen-limited conditions reveals intracellular sorting via vesicular transport systems.G3 (Bethesda, Md.) · 2025Article
- Pervasive Divergence in Protein Thermostability is Mediated by Both Structural Changes and Cellular Environments.Molecular biology and evolution · 2025Article
- Tracing the Origin and Evolution of the Fungal Mycophenolic Acid Biosynthesis Pathway.Genome biology and evolution · 2025Article
- RNA Polymerase II Activity Control of Gene Expression and Involvement in Disease.Journal of molecular biology · 2025Review
- Article
- GTP-dependent regulation of heterochromatin fluctuations at subtelomeric regions in Saccharomyces cerevisiae.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Comparative Transcriptome Profiles of the Response of Mycelia of the GenusJournal of fungi (Basel, Switzerland) · 2024Article
- Purine metabolism in plant pathogenic fungi.Frontiers in microbiology · 2024Review
- Quantitative analysis of transcription start site selection reveals control by DNA sequence, RNA polymerase II activity and NTP levels.Nature structural & molecular biology · 2024Article
- Interactions of GMP with Human Glrx3 and with Saccharomyces cerevisiae Grx3 and Grx4 Converge in the Regulation of the Gcn2 Pathway.Applied and environmental microbiology · 2020Article
- RNA Polymerase II CTD phosphatase Rtr1 fine-tunes transcription termination.PLoS genetics · 2020Article
- Inhibition of tRNA Gene Transcription by the Immunosuppressant Mycophenolic Acid.Molecular and cellular biology · 2019Article
- Comparative genomics of chytrid fungi reveal insights into the obligate biotrophic and pathogenic lifestyle of Synchytrium endobioticum.Scientific reports · 2019Article
- MoImd4 mediates crosstalk between MoPdeH-cAMP signalling and purine metabolism to govern growth and pathogenicity in Magnaporthe oryzae.Molecular plant pathology · 2019Article
- Spt6 Association with RNA Polymerase II Directs mRNA Turnover During Transcription.Molecular cell · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
IMP dehydrogenase (IMPDH) catalyzes the rate-limiting step in the de novo synthesis of GTP. Yeast with mutations in the transcription elongation machinery are sensitive to inhibitors of this enzyme such as 6-azauracil and mycophenolic acid, at least partly because of their inability to transcriptionally induce IMPDH. To understand the molecular basis of this drug-sensitive phenotype, we have dissected the expression and function of a four-gene family in yeast called IMD1 through IMD4. We show here that these family members are distinct, despite a high degree of amino acid identity between the proteins they encode. Extrachromosomal copies of IMD1, IMD3, or IMD4 could not rescue the drug-sensitive phenotype of IMD2 deletants. When overexpressed, IMD3 or IMD4 weakly compensated for deletion of IMD2. IMD1 is transcriptionally silent and bears critical amino acid substitutions compared with IMD2 that destroy its function, offering strong evidence that it is a pseudogene. The simultaneous deletion of all four IMD genes was lethal unless growth media were supplemented with guanine. This suggests that there are no other essential functions of the IMPDH homologs aside from IMP dehydrogenase activity. Although neither IMD3 nor IMD4 could confer drug resistance to cells lacking IMD2, either alone was sufficient to confer guanine prototrophy. The special function of IMD2 was provided by its ability to be transcriptionally induced and the probable intrinsic drug resistance of its enzymatic activity.
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