Title: Dissection of DNA damage responses using multiconditional genetic interaction maps.
Authors: Guénolé, Aude; Srivas, Rohith; Vreeken, Kees; Wang, Ze Zhong; Wang, Shuyi; Krogan, Nevan J; Ideker, Trey; van Attikum, Haico
Published In Mol Cell, (2013 Jan 24)
Abstract: To protect the genome, cells have evolved a diverse set of pathways designed to sense, signal, and repair multiple types of DNA damage. To assess the degree of coordination and crosstalk among these pathways, we systematically mapped changes in the cell's genetic network across a panel of different DNA-damaging agents, resulting in ~1,800,000 differential measurements. Each agent was associated with a distinct interaction pattern, which, unlike single-mutant phenotypes or gene expression data, has high statistical power to pinpoint the specific repair mechanisms at work. The agent-specific networks revealed roles for the histone acetyltranferase Rtt109 in the mutagenic bypass of DNA lesions and the neddylation machinery in cell-cycle regulation and genome stability, while the network induced by multiple agents implicates Irc21, an uncharacterized protein, in checkpoint control and DNA repair. Our multiconditional genetic interaction map provides a unique resource that identifies agent-specific and general DNA damage response pathways.
PubMed ID: 23273983
MeSH Terms: Cell Cycle Checkpoints/genetics; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Chromatin Assembly and Disassembly/genetics; DNA Damage*; DNA Repair/genetics; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Endonucleases/genetics; Endonucleases/metabolism; Epistasis, Genetic*; Gene Knockout Techniques; Gene Regulatory Networks; Genome, Fungal; Genomic Instability; Histone Acetyltransferases/genetics; Histone Acetyltransferases/metabolism; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Phosphoprotein Phosphatases/genetics; Phosphoprotein Phosphatases/metabolism; Protein Interaction Mapping; Protein Processing, Post-Translational; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Saccharomyces cerevisiae/genetics*; Saccharomyces cerevisiae/metabolism