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 ensu…
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Literature broadly has reported common co-regulation of genes in protein complexes at both transcription and translational levels.
“This is a unique finding since literature broadly has reported common co-regulation of genes in protein complexes at both transcription and translational levels96–102.”
From EXOSC3 G191 Variants Trigger System-Wide Recalibration of RNA Processing Machinery (2026) · cites this paper as [99]
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- 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., Ding, H., Xu, H., Han, J., Ingvarsdottir, K., Cheng, B., Andrews, B., Boone, C., Berger, S. L., Hieter, P., Zhang, Z., Brown, G. W., Ingles, C. J., Emili, A., Allis, C. D., Toczyski, D. P., Weissman, J. S., Greenblatt, J. F., & Krogan, N. J.
- Affiliations
- University of California, San Francisco (US)
- QB3 (US)
- University of Toronto (CA)
- Rockefeller University (US)
- Mayo Clinic (US)
- The Wistar Institute (US)
- University of British Columbia (CA)
- Corresponding author
- Weissman, Jonathan S.
- Greenblatt, Jack F.
- ORCID
- Collins, Sean R.
- Miller, Kyle M.
- Roguev, Assen
- Fillingham, Jeffrey
- Schuldiner, Maya
- Gebbia, Marinella
- Recht, Judith
- Xu, Hong
- Han, Junhong
- Ingvarsdottir, Kristin
- Andrews, Brenda
- Boone, Charles
- Berger, Shelley L.
- Zhang, Zhiguo
- Brown, Grant W.
- Emili, Andrew
- Allis, C. David
- Toczyski, David P.
- Weissman, Jonathan S.
- Greenblatt, Jack F.
- Krogan, Nevan J.
- Venue
- Nature
- Published
- 2007-02-21
- Volume
- 446
- Issue
- 7137
- Pages
- 806-810
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2062185406
- Cited by
- 869
- References
- 2
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 10 · 2023: 19 · 2022: 16 · 2021: 25 · 2020: 21 · 2019: 36 · 2018: 29 · 2017: 35 · 2016: 31 · 2015: 43 · 2014: 45 · 2013: 76 · 2012: 77
- FWCI
- 38.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- genetic interactions, protein complexes, Saccharomyces cerevisiae, chromosome biology, Mediator complex, Rtt109, histone acetyltransferase, Asf1, ubiquitin ligase, DNA replication, DNA repair, transcriptional regulation
- MeSH terms
- Acetylation, DNA Repair, DNA Replication, Epistasis, Genetic, Histones, Protein Binding, ROC Curve, Saccharomyces cerevisiae, Transcription, Genetic, Chromosomes, Fungal, Chromosome Segregation, Saccharomyces cerevisiae Proteins, Multiprotein Complexes
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