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

• 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; Deoxyribonucleic acid; Diverse techniques; DNA; 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; Humanities and Social Sciences; letter; Molecular and cellular biology; multidisciplinary; 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; Science; Science (multidisciplinary); transcription (genetics); Transcription, Genetic; ubiquitin-protein ligase; Yeast; Yeasts
• ISSN: 0028-0836; 1476-4687; 1476-4679
• DOI: 10.1038/nature05649

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.