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

Sean R. Collins, Kyle M. Miller, Nancy L. Maas, Assen Roguev, Jeffrey Fillingham, Clement S. Chu, Maya Schuldiner, Marinella Gebbia, Judith Recht, Michael Shales, Huiming Ding, Hong Xu, Junhong Han, Kristin Ingvarsdottir, Benjamin Cheng, Brenda Andrews, Charles Boone, Shelley L. Berger, Phil Hieter, Zhiguo ZhangGrant W. Brown, C. James Ingles, Andrew Emili, C. David Allis, David P. Toczyski, Jonathan S. Weissman, Jack F. Greenblatt, Nevan J. Krogan

Research output: Contribution to journalArticle

656 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)806-810
Number of pages5
JournalNature
Volume446
Issue number7137
DOIs
StatePublished - Apr 12 2007

ASJC Scopus subject areas

  • General

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