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Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map.


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.

Pubmed ID: 17314980


  • Collins SR
  • Miller KM
  • Maas NL
  • Roguev A
  • Fillingham J
  • Chu CS
  • Schuldiner M
  • Gebbia M
  • Recht J
  • Shales M
  • Ding H
  • Xu H
  • Han J
  • Ingvarsdottir K
  • Cheng B
  • Andrews B
  • Boone C
  • Berger SL
  • Hieter P
  • Zhang Z
  • Brown GW
  • Ingles CJ
  • Emili A
  • Allis CD
  • Toczyski DP
  • Weissman JS
  • Greenblatt JF
  • Krogan NJ



Publication Data

April 12, 2007

Associated Grants


Mesh Terms

  • Acetylation
  • Chromosome Segregation
  • Chromosomes, Fungal
  • DNA Repair
  • DNA Replication
  • Epistasis, Genetic
  • Histones
  • Multiprotein Complexes
  • Protein Binding
  • ROC Curve
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription, Genetic