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Global response of Saccharomyces cerevisiae to an alkylating agent
Open accessAbstract
DNA chip technology enables simultaneous examination of how ≈6,200 Saccharomyces cerevisiae gene transcript levels, representing the entire genome, respond to environmental change. By using chips bearing oligonucleotide arrays, we show that, after exposure to the alkylating agent methyl methanesulfonate, ≈325 gene transcript levels are increased and ≈76 are decreased. Of the 21 genes that already were known to be induced by a DNA-damaging agent, 18 can be scored as inducible in this data set, and surprisingly, most of the newly identified inducible genes are induced even more strongly than these 18. We examined 42 responsive and 8 nonresponsive ORFs by conventional Northern blotting, and 48 of these 50 ORFs responded as they did by DNA chip analysis, with magnitudes displaying a correlation coefficient of 0.79. Responsive genes fall into several expected and many unexpected categories. Evidence for the induction of a program to eliminate and replace alkylated proteins is presented.
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“Indeed, approximately 5% of the yeast genome is upregulated in response to various DNA-damaging agents (15, 23, 24).”
From A Role for Checkpoint Kinase-Dependent Rad26 Phosphorylation in Transcription-Coupled DNA Repair in Saccharomyces cerevisiae (2010) · cites this paper as [24]
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“Although our study in the mouse liver examines alkylation-induced transcriptional reprogramming in repair-deficient mice, they are mirrored by studies in Saccharomyces cerevisiae that similarly showed transcriptional induction of the UPR by alkylation treatment (19, 38).”
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BackgroundGenetic interaction screens advance in reversePreprint
Komili, S., & Roth, F. P. (2007) · Genes & Development · doi:10.1101/gad.1512707 · Cited by 10
“…constant despite changes in extracellular conditions (Herruer et al. 1987), oligo arrays revealed that the expression levels of many duplicated ribosomal protein genes change independently in response to MMS (Jelinsky and Samson 1999; S. Komili, N.G. Farny, F.P. Roth, and P.A. Silver, in prep.).”
BackgroundGenome expression on the World Wide Web
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“Over 30% of all yeast genes responded toMMS treatment, and they representedmultiple functional categories ( Jelinsky & Samson, 1999; Jelinsky et al., 2000).”
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Self-citationStructure of Ddi2, a highly inducible detoxifying metalloenzyme from Saccharomyces cerevisiae
Li, J., Jia, Y., Lin, A., Hanna, M. D., Chelico, L., Xiao, W., & Moore, S. A. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.006394 · Cited by 9
“alignment search tool; Pde, phosphodiesterase; PDB, Protein Data Bank; MMS, methyl methanesulfonate; GST, glutathione S-transferase. croARTICLE 10674 J. Biol.”
BackgroundInfluentialDeletion of yeast TPK1 reduces the efficiency of non-homologous end joining DNA repair
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“Jelinsky and Samson (1999) presented evidence in S. cerevisiae that treatment with alkylating agents induced transcription of genes involved in eliminating and replacing damaged proteins.”
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“MMS is also well described to reprogram gene expression patterns (69, 70), which will also lead to alteration of protein abundances and ubiquitylation.”
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“Unlike NQO, MMS does not directly produce ROS but instead causes DNA alkylation damage, leading to single-strand breaks and DSBs ( 80 ,81 ).”
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MethodDNA Microarrays: An Overview of Technologies and Applications to Toxicology
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“…mammalian cells have demonstrated that a reproducible subset of genes will show altered expression in response to specific conditions such as anoxia, nutrient deprivation, exposure to alkylating agents, and chemotherapeutic agents (DeRisi et al., 1997; Iyer et al., 1999; Jelinsky and Samson, 1999).”
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“…ciliate Oxytricha granulifera (Palmedo and Ammermann 1997), the expression of CCTθ induced in the ciliate Tetrahymena pyriformis by colchicine treatment (Domingues et al. 1999), and CCT8 expression in response to an alkylating agent in the yeast Saccharomyces cerevisiae (Jelinsky and Samson 1999).”
BackgroundMolecular Mechanisms of Livestock Adaptation
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“Moreover, this study also elucidated the key cellular defense mechanisms involved in eliminating and replacing alkylated proteins in the cell [25].”
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“Biotin labeled cRNA was prepared from cDNA using in vitro transcription (INV) with an Enzo Bioarray High Yield RNA Transcript Labeling Kit (Affymetrix, Inc., Santa Clara, CA), and then cRNA was randomly fragmented into 35–200 bases (Jelinsky and Samson, 1999).”
MethodDifferential regulation of gene expression by RNA polymerase II in response to DNA damage
Heo, J., Jeong, S.-J., Seol, J.-W., Kim, H., Han, J.-W., Lee, H. W., & Cho, E. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.10.101 · Cited by 4
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“One dataset contains 6335 genes with 121 conditions which were obtained by combining expression profiles from several gene expression experiments [5][21][26-31].”
MethodProteome analysis of Saccharomyces cerevisiae after methyl methane sulfonate (MMS) treatment
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“…leading to depleted deoxyribonucleoside triphosphate pools that prevent DNA replication) (Elford 1968; Yarbro 1992), methyl methanesulfonate (MMS, a DNA-alkylating agent that methylates bases and can induce a variety of lesions, including strand breaks) (Jelinsky and Samson 1999; Kim et al.”
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“The expression of a number of NER proteins is upregulated as a result of DNA damage; however, once the DNA damage is repaired and the proteins are no longer needed, they are degraded to restore basal levels [1, 34].”
BackgroundSynthetic oligonucleotide combinatorial libraries and their applications
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“…al. 1997; ter Linde et al. 1999; Kuhn et al. 2001), during sporulation (Chu et al. 1998), during the cell cycle (Cho et al. 1998; Spellman et al. 1998) or in response to conditions or treatments of interest, such as chemical or environmental agents (Jelinsky and Samson 1999; Jelinsky et al. 2000).”
BackgroundAccounting for Programmed Ribosomal Frameshifting in the Computation of Codon Usage Bias Indices
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“At present, commercially manufactured oligonucleotide chips in which tens of thousands of oligonucleotides representing all the genes of a genome and spotted in a small area are available for several organisms including Saccharomyces and Drosophila [Jelinsky and Samson, 1999; McDonald and Rosbash, 2001].”
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Cellular and Molecular Responses to Alkylation Damage in DNA
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Assembly of Slx4 Checkpoint Signaling Complexes Behind Stressed DNA Replication Forks
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Metadata
- Authors
- Jelinsky, S. A., & Samson, L. D.
- Affiliations
- Harvard University (US)
- Corresponding author
- Samson, Leona D.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-02-16
- Volume
- 96
- Issue
- 4
- Pages
- 1486-1491
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC15489
- OpenAlex
- W2155675863
- Cited by
- 419
- References
- 36
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 11 · 2014: 10 · 2013: 8 · 2012: 11
- FWCI
- 17.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01hg001323-03)
- National Human Genome Research Institute (P01 HG 01323)
- National Cancer Institute (CA-55042, CA09078, T32CA009078, R01CA055042)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Saccharomyces cerevisiae, methyl methanesulfonate, alkylating agents, DNA damage response, gene expression profiling, transcriptome, DNA repair genes
- MeSH terms
- Alkylating Agents, DNA Damage, Fungal Proteins, Genes, Fungal, Methyl Methanesulfonate, Saccharomyces cerevisiae, Transcription, Genetic, Open Reading Frames, Genome, Fungal
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