Functional wiring of the yeast kinome revealed by global analysis of genetic network motifs

Sara Sharifpoor, Dewald Van Dyk, Michael Costanzo, Anastasia Baryshnikova, Helena Friesen, Alison C. Douglas, Ji Young Youn, Benjamin VanderSluis, Chad L. Myers, Balázs Papp, Charles Boone, Brenda J. Andrews

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)791-801
Number of pages11
JournalGenome research
Volume22
Issue number4
DOIs
StatePublished - Apr 2012

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