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...

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Bibliographic Details
Published in:Nature 2007-04, Vol.446 (7137), p.806-810
Main Authors: Collins, S.R, Miller, K.M, Maas, N.L, Roguev, A, Fillingham, J, Chu, C.S, Schuldiner, M, Gebbia, M, Recht, J, Shales, M
Format: Article
Language:English
Subjects:
Acetylation
Biological and medical sciences
Cellular biology
Chromosome Segregation
Chromosomes
Chromosomes, Fungal - genetics
Chromosomes, Fungal - metabolism
Diverse techniques
DNA Repair
DNA Replication
epistasis
Epistasis, Genetic
epistatic miniarray profile
Fundamental and applied biological sciences. Psychology
gene expression regulation
genes
Genetics
histone acetyltransferase
Histones - metabolism
Molecular and cellular biology
Multiprotein Complexes - chemistry
Multiprotein Complexes - genetics
Multiprotein Complexes - metabolism
Protein Binding
Proteins
ROC Curve
Saccharomyces cerevisiae
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
transcription (genetics)
Transcription, Genetic
ubiquitin-protein ligase
Yeast
yeasts
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Summary: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.
ISSN:0028-0836
1476-4687
1476-4679
DOI:10.1038/nature05649