Searching across hundreds of databases
Mec1ATR mediates the DNA damage response (DDR), integrating chromosomal signals and mechanical stimuli. We show that the PP2A phosphatases, ceramide-activated enzymes, couple cell metabolism with the DDR. Using genomic screens, metabolic analysis, and genetic and pharmacological studies, we found that PP2A attenuates the DDR and that three metabolic circuits influence the DDR by modulating PP2A activity. Irc21, a putative cytochrome b5 reductase that promotes the condensation reaction generating dihydroceramides (DHCs), and Ppm1, a PP2A methyltransferase, counteract the DDR by activating PP2A; conversely, the nutrient-sensing TORC1-Tap42 axis sustains DDR activation by inhibiting PP2A. Loss-of-function mutations in IRC21, PPM1, and PP2A and hyperactive tap42 alleles rescue mec1 mutants. Ceramides synergize with rapamycin, a TORC1 inhibitor, in counteracting the DDR. Hence, PP2A integrates nutrient-sensing and metabolic pathways to attenuate the Mec1ATR response. Our observations imply that metabolic changes affect genome integrity and may help with exploiting therapeutic options and repositioning known drugs.
Pubmed ID: 28648781 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets Histone H2A
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Goat Mouse IgG (H L)-HRP Conjugate
View all literature mentionsThis monoclonal targets Viral V5-TAG
View all literature mentionsThis monoclonal targets c-Myc
View all literature mentionsThis polyclonal targets Histone H2A (phospho S129) antibody - ChIP Grade
View all literature mentionsOpen source and enterprise ready professional software for R statistical computing environment. Integrated development environment for R. Includes console, syntax highlighting editor that supports direct code execution, as well as tools for plotting, history, debugging and workspace management. Available in open source and commercial editions and runs on desktop Windows, Mac, and Linux or in browser connected to RStudio Server or RStudio Server Pro (Debian/Ubuntu, RedHat/CentOS, and SUSE Linux).
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsThis monoclonal targets c-Myc
View all literature mentionsThis monoclonal targets Viral V5-TAG
View all literature mentionsThis polyclonal targets Histone H2A (phospho S129) antibody - ChIP Grade
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
