Cited by 542DNA Repair MechanismsFungal and yeast genetics researchBacterial Genetics and Biotechnology

Genomic Expression Responses to DNA-damaging Agents and the Regulatory Role of the Yeast ATR Homolog Mec1p

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Gasch, Audrey P., Huang, Mingxia, Metzner, Sandra, Botstein, David, Elledge, Stephen J., Brown, Patrick O.·2001·Molecular Biology of the Cell

Abstract

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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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
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
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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