title: Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map.
abstract: Defining the functional relationships between proteins is critical for understanding virtually all aspects of cell biology. Large-scale identification of protein complexes has provided one important step towards this goal; however, even knowledge of the stoichiometry, affinity and lifetime of every protein-protein interaction would not reveal the functional relationships between and within such complexes. Genetic interactions can provide functional information that is largely invisible to protein-protein interaction data sets. Here we present an epistatic miniarray profile (E-MAP) consisting of quantitative pairwise measurements of the genetic interactions between 743 Saccharomyces cerevisiae genes involved in various aspects of chromosome biology (including DNA replication/repair, chromatid segregation and transcriptional regulation). This E-MAP reveals that physical interactions fall into two well-represented classes distinguished by whether or not the individual proteins act coherently to carry out a common function. Thus, genetic interaction data make it possible to dissect functionally multi-protein complexes, including Mediator, and to organize distinct protein complexes into pathways. In one pathway defined here, we show that Rtt109 is the founding member of a novel class of histone acetyltransferases responsible for Asf1-dependent acetylation of histone H3 on lysine 56. This modification, in turn, enables a ubiquitin ligase complex containing the cullin Rtt101 to ensure genomic integrity during DNA replication.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Collins
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Miller
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Maas
authors.forename: Assen
authors.initials: A
authors.lastname: Roguev
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fillingham
authors.forename: Clement S
authors.initials: CS
authors.lastname: Chu
authors.forename: Maya
authors.initials: M
authors.lastname: Schuldiner
authors.forename: Marinella
authors.initials: M
authors.lastname: Gebbia
authors.forename: Judith
authors.initials: J
authors.lastname: Recht
authors.forename: Michael
authors.initials: M
authors.lastname: Shales
authors.forename: Huiming
authors.initials: H
authors.lastname: Ding
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Junhong
authors.initials: J
authors.lastname: Han
authors.forename: Kristin
authors.initials: K
authors.lastname: Ingvarsdottir
authors.forename: Benjamin
authors.initials: B
authors.lastname: Cheng
authors.forename: Brenda
authors.initials: B
authors.lastname: Andrews
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
authors.forename: Shelley L
authors.initials: SL
authors.lastname: Berger
authors.forename: Phil
authors.initials: P
authors.lastname: Hieter
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Grant W
authors.initials: GW
authors.lastname: Brown
authors.forename: C James
authors.initials: CJ
authors.lastname: Ingles
authors.forename: Andrew
authors.initials: A
authors.lastname: Emili
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
authors.forename: David P
authors.initials: DP
authors.lastname: Toczyski
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Weissman
authors.forename: Jack F
authors.initials: JF
authors.lastname: Greenblatt
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
mesh_terms: D000107:Acetylation; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D004843:Epistasis, Genetic; D006657:Histones / Q000378:metabolism; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012372:ROC Curve; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins