title: Dosage suppression genetic interaction networks enhance functional wiring diagrams of the cell.
abstract: Dosage suppression is a genetic interaction in which overproduction of one gene rescues a mutant phenotype of another gene. Although dosage suppression is known to map functional connections among genes, the extent to which it might illuminate global cellular functions is unclear. Here we analyze a network of interactions linking dosage suppressors to 437 essential genes in yeast. For 424 genes, we curated interactions from the literature. Analyses revealed that many dosage suppression interactions occur between functionally related genes and that the majority do not overlap with other types of genetic or physical interactions. To confirm the generality of these network properties, we experimentally identified dosage suppressors for 29 genes from pooled populations of temperature-sensitive mutant cells transformed with a high-copy molecular-barcoded open reading frame library, MoBY-ORF 2.0. We classified 87% of the 1,640 total interactions into four general types of suppression mechanisms, which provided insight into their relative frequencies. This work suggests that integrating the results of dosage suppression studies with other interaction networks could generate insights into the functional wiring diagram of a cell.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Leslie
authors.initials: L
authors.lastname: Magtanong
authors.forename: Cheuk Hei
authors.initials: CH
authors.lastname: Ho
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Barker
authors.forename: Wei
authors.initials: W
authors.lastname: Jiao
authors.forename: Anastasia
authors.initials: A
authors.lastname: Baryshnikova
authors.forename: Sondra
authors.initials: S
authors.lastname: Bahr
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Smith
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Heisler
authors.forename: John S
authors.initials: JS
authors.lastname: Choy
authors.forename: Elena
authors.initials: E
authors.lastname: Kuzmin
authors.forename: Kerry
authors.initials: K
authors.lastname: Andrusiak
authors.forename: Anna
authors.initials: A
authors.lastname: Kobylianski
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Costanzo
authors.forename: Munira A
authors.initials: MA
authors.lastname: Basrai
authors.forename: Guri
authors.initials: G
authors.lastname: Giaever
authors.forename: Corey
authors.initials: C
authors.lastname: Nislow
authors.forename: Brenda
authors.initials: B
authors.lastname: Andrews
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
mesh_terms: D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D003663:Decision Trees; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D015723:Gene Library; D053263:Gene Regulatory Networks; D020043:Genes, Essential; D005800:Genes, Fungal; D059014:High-Throughput Nucleotide Sequencing; D018386:Kinetochores / Q000378:metabolism; D009154:Mutation; D016366:Open Reading Frames; D010641:Phenotype; D025941:Protein Interaction Mapping / Q000379:methods; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013489:Suppression, Genetic; D014158:Transcription, Genetic
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases