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Exploration of Essential Gene Functions via Titratable Promoter Alleles
Open accessAbstract
Nearly 20% of yeast genes are required for viability, hindering genetic analysis with knockouts. We created promoter-shutoff strains for over two-thirds of all essential yeast genes and subjected them to morphological analysis, size profiling, drug sensitivity screening, and microarray expression profiling. We then used this compendium of data to ask which phenotypic features characterized different functional classes and used these to infer potential functions for uncharacterized genes. We identified genes involved in ribosome biogenesis (HAS1, URB1, and URB2), protein secretion (SEC39), mitochondrial import (MIM1), and tRNA charging (GSN1). In addition, apparent negative feedback transcriptional regulation of both ribosome biogenesis and the proteasome was observed. We furthermore show that these strains are compatible with automated genetic analysis. This study underscores the importance of analyzing mutant phenotypes and provides a resource to complement the yeast knockout collection.
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“In general, essential genes participated in ~5-fold more negative and positive interactions than nonessential genes, confirming previous estimates (Fig. 5A)(24).”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [24]
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“First, consistent with the results of our previous smaller scale surveys (1, 24), essential genes are major hubs and form the basic scaffold of the global genetic interaction network.”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [24]
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Cited by
Sorted by citations
A global genetic interaction network maps a wiring diagram of cellular function
Costanzo, M., VanderSluis, B., Koch, E. N., Baryshnikova, A., Pons, C., Tan, G., Wang, W., Usaj, M., Hanchard, J., Lee, S. D., et al. (2016) · Science · doi:10.1126/science.aaf1420 · Cited by 1,240
“First, consistent with the results of our previous smaller-scale surveys (1, 24), essential genes are major hubs and form the basic scaffold of the global genetic interaction network.”
ResultSelf-citationSgs1 Helicase and Two Nucleases Dna2 and Exo1 Resect DNA Double-Strand Break Ends
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“DAmP utilizes simple, PCR-based homologous recombination to disrupt the natural 3#UTR by insertion of an antibiotic-resistance marker, thus greatly destabilizing the corresponding messages (Muhlrad and Parker, 1999).”
MethodSelf-citationGene essentiality and synthetic lethality in haploid human cells
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Metadata
- Authors
- Mnaimneh, S., Davierwala, A. P., Haynes, J., Moffat, J., Peng, W.-T., Zhang, W., Yang, X., Pootoolal, J., Chua, G., Lopez, A., Trochesset, M., Morse, D., Krogan, N. J., Hiley, S. L., Li, Z., Morris, Q., Grigull, J., Mitsakakis, N., Roberts, C. J., Greenblatt, J. F., Boone, C., Kaiser, C. A., Andrews, B. J., & Hughes, T. R.
- Affiliations
- University of Toronto (CA)
- Massachusetts Institute of Technology (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Hughes, Timothy R
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 118
- Issue
- 1
- Pages
- 31-44
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1974220691
- Cited by
- 604
- References
- 64
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 17 · 2023: 15 · 2022: 22 · 2021: 21 · 2020: 14 · 2019: 17 · 2018: 17 · 2017: 21 · 2016: 23 · 2015: 26 · 2014: 30 · 2013: 28 · 2012: 32
- FWCI
- 14.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3303 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- essential genes, Saccharomyces cerevisiae, gene function prediction, ribosome biogenesis, protein secretion, mitochondrial protein import, aminoacylation, proteasome, mutant phenotypes
- MeSH terms
- Alleles, Pharmaceutical Preparations, Genes, Fungal, Mitochondria, Models, Genetic, Promoter Regions, Genetic, Protein Processing, Post-Translational, Ribosomal Proteins, RNA, Transfer, Saccharomyces cerevisiae, Transcription, Genetic, Gene Expression Regulation, Fungal, Gene Deletion, Genes, Essential, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Feedback, Physiological, Saccharomyces cerevisiae Proteins
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