Genomic Expression Responses to DNA-damaging Agents and the Regulatory Role of the Yeast ATR Homolog Mec1p
Open accessAbstract
Eukaryotic cells respond to DNA damage by arresting the cell cycle and modulating gene expression to ensure efficient DNA repair. The human ATR kinase and its homolog in yeast, MEC1, play central roles in transducing the damage signal. To characterize the role of the Mec1 pathway in modulating the cellular response to DNA damage, we used DNA microarrays to observe genomic expression inSaccharomyces cerevisiae responding to two different DNA-damaging agents. We compared the genome-wide expression patterns of wild-type cells and mutants defective in Mec1 signaling, includingmec1, dun1, and crt1 mutants, under normal growth conditions and in response to the methylating-agent methylmethane sulfonate (MMS) and ionizing radiation. Here, we present a comparative analysis of wild-type and mutant cells responding to these DNA-damaging agents, and identify specific features of the gene expression responses that are dependent on the Mec1 pathway. Among the hundreds of genes whose expression was affected by Mec1p, one set of genes appears to represent an MEC1-dependent expression signature of DNA damage. Other aspects of the genomic responses were independent of Mec1p, and likely independent of DNA damage, suggesting the pleiotropic effects of MMS and ionizing radiation. The complete data set as well as supplemental materials is available at http://www-genome.stanford.edu/mec1 .
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Approximately 5% of the yeast genome is upregulated in response to various DNA-damaging agents.
“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 <i>Saccharomyces cerevisiae</i> (2010) · cites this paper as [15]
Many of the DNA-damage-upregulated genes are regulated by Mec1, indicating involvement of the DNA damage checkpoint in the DNA damage-related transcriptional response.
“Many of these genes are regulated by Mec1, indicating an involvement of the DNA damage checkpoint in the DNA damage-related transcriptional response (15).”
From A Role for Checkpoint Kinase-Dependent Rad26 Phosphorylation in Transcription-Coupled DNA Repair in <i>Saccharomyces cerevisiae</i> (2010) · cites this paper as [15]
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- Authors
- Gasch, A. P., Huang, M., Metzner, S., Botstein, D., Elledge, S. J., & Brown, P. O.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- Department of Biochemistry and
- Departments of Biochemistry and
- Genetics, and
- Howard Hughes Medical Institute (US)
- Corresponding author
- Brown, Patrick O.
- Venue
- Molecular Biology of the Cell
- Published
- 2001-10
- Volume
- 12
- Issue
- 10
- Pages
- 2987-3003
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC60150
- OpenAlex
- W2162735386
- Cited by
- 542
- References
- 71
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 12 · 2021: 10 · 2020: 12 · 2019: 13 · 2018: 11 · 2017: 12 · 2016: 20 · 2015: 21 · 2014: 21 · 2013: 23 · 2012: 21
- FWCI
- 11.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Damon Runyon Cancer Research Foundation
- National Institutes of Health (5r01hg000983-06)
- National Human Genome Research Institute (HG-00983, HG-00450)
- National Institute of General Medical Sciences (GM-44664, GM46406, R37GM046406, R37GM044664, R01GM046406, R01GM044664)
- 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
- ATR kinase, DNA damage response, Saccharomyces cerevisiae, gene expression profiling, methyl methanesulfonate, ionizing radiation, Dun1, DNA repair, cell cycle arrest
- MeSH terms
- DNA Damage, DNA Repair, DNA, Fungal, Fungal Proteins, Methyl Methanesulfonate, Mutation, Protein Kinases, Radiation, Ionizing, Saccharomyces cerevisiae, Signal Transduction, Gene Expression Regulation, Fungal, Protein Serine-Threonine Kinases, Sequence Homology, Cell Cycle Proteins, Oligonucleotide Array Sequence Analysis, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins
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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.
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