Effect of passage number on cellular response to DNA-damaging agents: cell survival and gene expression

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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Faculty Opinions recommendation of A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1161238.621722 ◽

2009 ◽

Author(s):

Martin Fernandez-Zapico

Keyword(s):

Gene Expression ◽

Tumor Cell ◽

Cell Survival ◽

Gene Expression Signature ◽

Expression Signature ◽

Tumor Cell Survival

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Nanoparticle-plasma Membrane Interactions: Thermodynamics, Toxicity and Cellular Response

Current Medicinal Chemistry ◽

10.2174/0929867325666181112090648 ◽

2020 ◽

Vol 27 (20) ◽

pp. 3330-3345

Author(s):

Ana G. Rodríguez-Hernández ◽

Rafael Vazquez-Duhalt ◽

Alejandro Huerta-Saquero

Keyword(s):

Gene Expression ◽

Immune Responses ◽

Cellular Response ◽

Cellular Level ◽

Membrane Interactions ◽

Daily Lives ◽

Cellular Physiology ◽

Associated Proteins ◽

First Contact ◽

Insight Into

Nanomaterials have become part of our daily lives, particularly nanoparticles contained in food, water, cosmetics, additives and textiles. Nanoparticles interact with organisms at the cellular level. The cell membrane is the first protective barrier against the potential toxic effect of nanoparticles. This first contact, including the interaction between the cell membranes -and associated proteins- and the nanoparticles is critically reviewed here. Nanoparticles, depending on their toxicity, can cause cellular physiology alterations, such as a disruption in cell signaling or changes in gene expression and they can trigger immune responses and even apoptosis. Additionally, the fundamental thermodynamics behind the nanoparticle-membrane and nanoparticle-proteins-membrane interactions are discussed. The analysis is intended to increase our insight into the mechanisms involved in these interactions. Finally, consequences are reviewed and discussed.

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A gene expression signature associated with ‘‘K-Ras addiction’’ reveals regulators of EMT and tumor cell survival

Cancer Cell ◽

10.1016/j.ccell.2021.02.009 ◽

2021 ◽

Vol 39 (3) ◽

pp. 441-442

Author(s):

Anurag Singh ◽

Patricia Greninger ◽

Daniel Rhodes ◽

Louise Koopman ◽

Sheila Violette ◽

...

Keyword(s):

Gene Expression ◽

Tumor Cell ◽

Cell Survival ◽

Gene Expression Signature ◽

Expression Signature ◽

Tumor Cell Survival

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The oxen Gene of Drosophila Encodes a Homolog of Subunit 9 of Yeast Ubiquinol-Cytochrome c Oxidoreductase Complex: Evidence for Modulation of Gene Expression in Response to Mitochondrial Activity

Genetics ◽

10.1093/genetics/156.4.1727 ◽

2000 ◽

Vol 156 (4) ◽

pp. 1727-1736 ◽

Cited By ~ 2

Author(s):

Maxim V Frolov ◽

Elizaveta V Benevolenskaya ◽

James A Birchler

Keyword(s):

Gene Expression ◽

Cytochrome C ◽

Cellular Response ◽

Insertion Site ◽

Nuclear Gene ◽

Mutant Phenotype ◽

P Element ◽

Mitochondrial Activity ◽

Genes Encoding ◽

Subunit 9

Abstract A P-element insertion in the oxen gene, ox1, has been isolated in a search for modifiers of white gene expression. The mutation preferentially exerts a negative dosage effect upon the expression of three genes encoding ABC transporters involved in pigment precursor transport, white, brown, and scarlet. A precise excision of the P element reverts the mutant phenotype. Five different transcription units were identified around the insertion site. To distinguish a transcript responsible for the mutant phenotype, a set of deletions within the oxen region was generated. Analysis of gene expression within the oxen region in the case of deletions as well as generation of transgenic flies allowed us to identify the transcript responsible for oxen function. It encodes a 6.6-kD homolog of mitochondrial ubiquinol cytochrome c oxidoreductase (QCR9), subunit 9 of the bc1 complex in yeast. In addition to white, brown, and scarlet, oxen regulates the expression of three of seven tested genes. Thus, our data provide additional evidence for a cellular response to changes in mitochondrial function. The oxen mutation provides a model for the genetic analysis in multicellular organisms of the effect of mitochondrial activity on nuclear gene expression.

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Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation

Physiological Genomics ◽

10.1152/physiolgenomics.00157.2007 ◽

2008 ◽

Vol 32 (2) ◽

pp. 219-228 ◽

Cited By ~ 74

Author(s):

Adeel Safdar ◽

Nicholas J. Yardley ◽

Rodney Snow ◽

Simon Melov ◽

Mark A. Tarnopolsky

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Mrna Expression ◽

Protein Content ◽

Cellular Response ◽

Glycogen Synthesis ◽

Creatine Monohydrate ◽

Fat Free Mass ◽

Cell Swelling ◽

Short Term

Creatine monohydrate (CrM) supplementation has been shown to increase fat-free mass and muscle power output possibly via cell swelling. Little is known about the cellular response to CrM. We investigated the effect of short-term CrM supplementation on global and targeted mRNA expression and protein content in human skeletal muscle. In a randomized, placebo-controlled, crossover, double-blind design, 12 young, healthy, nonobese men were supplemented with either a placebo (PL) or CrM (loading phase, 20 g/day × 3 days; maintenance phase, 5 g/day × 7 days) for 10 days. Following a 28-day washout period, subjects were put on the alternate supplementation for 10 days. Muscle biopsies of the vastus lateralis were obtained and were assessed for mRNA expression (cDNA microarrays + real-time PCR) and protein content (Kinetworks KPKS 1.0 Protein Kinase screen). CrM supplementation significantly increased fat-free mass, total body water, and body weight of the participants ( P < 0.05). Also, CrM supplementation significantly upregulated (1.3- to 5.0-fold) the mRNA content of genes and protein content of kinases involved in osmosensing and signal transduction, cytoskeleton remodeling, protein and glycogen synthesis regulation, satellite cell proliferation and differentiation, DNA replication and repair, RNA transcription control, and cell survival. We are the first to report this large-scale gene expression in the skeletal muscle with short-term CrM supplementation, a response that suggests changes in cellular osmolarity.

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Pituitary adenylate cyclase-activating polypeptide stimulates both c-fos gene expression and cell survival in rat cerebellar granule neurons through activation of the protein kinase A pathway

Neuroscience ◽

10.1016/s0306-4522(97)00545-9 ◽

1998 ◽

Vol 84 (3) ◽

pp. 801-812 ◽

Cited By ~ 81

Author(s):

D Vaudry ◽

B.J Gonzalez ◽

M Basille ◽

Y Anouar ◽

A Fournier ◽

...

Keyword(s):

Gene Expression ◽

Protein Kinase ◽

Adenylate Cyclase ◽

Cell Survival ◽

Protein Kinase A ◽

Cerebellar Granule Neurons ◽

Granule Neurons ◽

Cerebellar Granule ◽

Pituitary Adenylate Cyclase ◽

Kinase A

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Multi-species transcriptome meta-analysis of the response to retinoic acid in vertebrates and comparative analysis of the effects of retinol and retinoic acid on gene expression in LMH cells

BMC Genomics ◽

10.1186/s12864-021-07451-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Clemens Falker-Gieske ◽

Andrea Mott ◽

Sören Franzenburg ◽

Jens Tetens

Keyword(s):

Gene Expression ◽

Retinoic Acid ◽

Cellular Response ◽

Homo Sapiens ◽

Meta Analysis ◽

Early Response ◽

Rna Seq ◽

Transcriptomic Response ◽

Time Points ◽

Lmh Cells

Abstract Background Retinol (RO) and its active metabolite retinoic acid (RA) are major regulators of gene expression in vertebrates and influence various processes like organ development, cell differentiation, and immune response. To characterize a general transcriptomic response to RA-exposure in vertebrates, independent of species- and tissue-specific effects, four publicly available RNA-Seq datasets from Homo sapiens, Mus musculus, and Xenopus laevis were analyzed. To increase species and cell-type diversity we generated RNA-seq data with chicken hepatocellular carcinoma (LMH) cells. Additionally, we compared the response of LMH cells to RA and RO at different time points. Results By conducting a transcriptome meta-analysis, we identified three retinoic acid response core clusters (RARCCs) consisting of 27 interacting proteins, seven of which have not been associated with retinoids yet. Comparison of the transcriptional response of LMH cells to RO and RA exposure at different time points led to the identification of non-coding RNAs (ncRNAs) that are only differentially expressed (DE) during the early response. Conclusions We propose that these RARCCs stand on top of a common regulatory RA hierarchy among vertebrates. Based on the protein sets included in these clusters we were able to identify an RA-response cluster, a control center type cluster, and a cluster that directs cell proliferation. Concerning the comparison of the cellular response to RA and RO we conclude that ncRNAs play an underestimated role in retinoid-mediated gene regulation.

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