Search Organism: All OrganismsArabidopsis thalianaBacillus subtilis 168Bos taurusCaenorhabditis elegansCanis familiarisDanio rerioDrosophila melanogasterEquus caballusEscherichia coli K12Gallus gallusHomo sapiensMacaca mulattaMus musculusNematostella vectensisOryza sativaPan troglodytesRattus norvegicusSaccharomyces cerevisiaeSchizosaccharomyces pombeStrongylocentrotus purpuratusTakifugu rubripesXenopus laevis home help / support contribute downloads mirrors about us Nucleic Acids Res. Feb (2008); 36(2):353-63 Cordycepin-hypersensitive growth links elevated polyphosphate levels to inhibition of poly-A- polymerase in Saccharomyces cerevisiae- Holbein S, Freimoser FM, Werner TP, Wengi A, Dichtl B Institute of Molecular Biology, University of Zurich, Zurich, Switzerland- Abstract: To identify genes involved in poly-A- metabolism, we screened the yeast gene deletion collection for growth defects in the presence of cordycepin -3'-deoxyadenosine-, a precursor to the RNA chain terminating ATP analog cordycepin triphosphate- Deltapho80 and Deltapho85 strains, which have a constitutively active phosphate-response pathway, were identified as cordycepin hypersensitive- We show that inorganic polyphosphate -poly P- accumulated in these strains and that poly P is a potent inhibitor of poly-A- polymerase activity in vitro- Binding analyses of poly P and yeast Pap1p revealed an interaction with a k-D- in the low nanomolar range- Poly P also bound mammalian poly-A- polymerase, however, with a 10-fold higher k-D- compared to yeast Pap1p- Genetic tests with double mutants of Deltapho80 and other genes involved in phosphate homeostasis and poly P accumulation suggest that poly P contributed to cordycepin hypersensitivity- Synergistic inhibition of mRNA synthesis through poly P-mediated inhibition of Pap1p and through cordycepin-mediated RNA chain termination may thus account for hypersensitive growth of Deltapho80 and Deltapho85 strains in the presence of the chain terminator- Consistent with this, a mutation in the 3'-end formation component rna14 was synthetic lethal in combination with Deltapho80- Based on these observations, we suggest that binding of poly P to poly-A- polymerase negatively regulates its activity- [PUBMED: 18033801] Copyright © 2009, Tyers Lab, The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, All Rights Reserved. terms and conditions - privacy policy - Osprey Network Visualization System BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9.