Author:
Sharifpoor Sara,van Dyk Dewald,Costanzo Michael,Baryshnikova Anastasia,Friesen Helena,Douglas Alison C.,Youn Ji-Young,VanderSluis Benjamin,Myers Chad L.,Papp Balázs,Boone Charles,Andrews Brenda J.
Abstract
A combinatorial genetic perturbation strategy was applied to interrogate the yeast kinome on a genome-wide scale. We assessed the global effects of gene overexpression or gene deletion to map an integrated genetic interaction network of synthetic dosage lethal (SDL) and loss-of-function genetic interactions (GIs) for 92 kinases, producing a meta-network of 8700 GIs enriched for pathways known to be regulated by cognate kinases. Kinases most sensitive to dosage perturbations had constitutive cell cycle or cell polarity functions under standard growth conditions. Condition-specific screens confirmed that the spectrum of kinase dosage interactions can be expanded substantially in activating conditions. An integrated network composed of systematic SDL, negative and positive loss-of-function GIs, and literature-curated kinase–substrate interactions revealed kinase-dependent regulatory motifs predictive of novel gene-specific phenotypes. Our study provides a valuable resource to unravel novel functional relationships and pathways regulated by kinases and outlines a general strategy for deciphering mutant phenotypes from large-scale GI networks.
Publisher
Cold Spring Harbor Laboratory
Subject
Genetics(clinical),Genetics
Cited by
65 articles.
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