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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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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)
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- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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