Shimada K~Gasser SM, 2013

Pubmed ID 24035500
Title TORC2 signaling pathway guarantees genome stability in the face of DNA strand breaks.
Authors Kenji Shimada, Ireos Filipuzzi, Michael Stahl, Stephen B Helliwell, Christian Studer, Dominic Hoepfner, Andrew Seeber, Robbie Loewith, N Rao Movva, Susan M Gasser
Abstract A chemicogenetic screen was performed in budding yeast mutants that have a weakened replication stress response. This identified an inhibitor of target of rapamycin (TOR) complexes 1 and 2 that selectively enhances the sensitivity of sgs1Δ cells to hydroxyurea and camptothecin. More importantly, the inhibitor has strong synthetic lethality in combination with either the break-inducing antibiotic Zeocin or ionizing radiation, independent of the strain background. Lethality correlates with a rapid fragmentation of chromosomes that occurs only when TORC2, but not TORC1, is repressed. Genetic inhibition of Tor2 kinase, or its downstream effector kinases Ypk1/Ypk2, conferred similar synergistic effects in the presence of Zeocin. Given that Ypk1/Ypk2 controls the actin cytoskeleton, we tested the effects of actin modulators latrunculin A and jasplakinolide. These phenocopy TORC2 inhibition on Zeocin, although modulation of calcineurin-sensitive transcription does not. These results implicate TORC2-mediated actin filament regulation in the survival of low levels of DNA damage.
Citation Mol. Cell 2013; 51:829-39

Datasets

Download the list of datasets
Paper Phenotype Condition Medium Collection Tested mutants Data Details
Shimada K~Gasser SM, 2013 growth (pooled culture) NVP-BHS345 [25 uM] SC het ~5,797 Quantitative
Shimada K~Gasser SM, 2013 growth (pooled culture) NVP-BHS345 [18 uM] SC hom N/A Quantitative

Curation history

Data

Sept. 21, 2020 Request sent.
Sept. 21, 2020 To request.
Sept. 23, 2020 Ready to load.

Tested strains

Sept. 21, 2020 Request sent.
Sept. 21, 2020 To request.
Sept. 23, 2020 Ready to load.