Alkylation-induced gene expression changes in Aag knock-out liver
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE115254 | GEO | 2018/06/04
REPOSITORIES: GEO
Similar Datasets
Project description:We are investigating the transcriptional response of mice that are wt or null for Aag in response to alkylating agent MMS We used microarrays to detail the global programme of gene expression response due to MMS exposure in a DNA repair proficient or deficient mouse Keywords: timepoint
2009-02-04 | GSE11252 | GEO
Project description:We are investigating the transcriptional response of mice that are wt or null for Aag in response to alkylating agent MMS; We used microarrays to detail the global programme of gene expression response due to MMS exposure in a DNA repair proficient or deficient mouse Experiment Overall Design: Mice (WT and Aag null) were treated with MMS and livers extracted at 6, 12, 24, and 48 hours
2009-02-21 | E-GEOD-11252 | biostudies-arrayexpress
Project description:Alkylation-induced gene expression changes in Aag knock-out liver
| PRJNA474379 | ENA
Project description:DNA base damage is an important contributor to genome instability, but how the formation and repair of these lesions is affected by the genomic landscape is unknown. Here we describe genome-wide maps of DNA base damage, repair, and mutagenesis at single nucleotide resolution in yeast treated with the alkylating agent methyl methanesulfonate (MMS). Analysis of these maps revealed that base excision repair (BER) of alkylation damage is significantly modulated by chromatin, with faster repair in nucleosome free regions, and slower repair and higher mutation density within strongly positioned nucleosomes. Both the translational and rotational settings of lesions within nucleosomes significantly influence BER efficiency; moreover, this effect is asymmetric relative to the nucleosome dyad and is regulated by histone modifications. Our data also indicate that MMS-induced A mutations are significantly enriched on the non-transcribed strand (NTS) of yeast genes, particularly in BER-deficient strains, due to higher damage formation on the NTS and transcription-coupled repair of the transcribed strand (TS). These findings reveal the influence of chromatin on repair and mutagenesis of base lesions on a genome-wide scale, and suggest a novel mechanism for transcription-associated mutation asymmetry, which is frequently observed in human cancers.
2017-08-10 | GSE98031 | GEO
Project description:Ribosome profiling was used to investigate how Schizosaccharomcyes pombe cells modulate gene expression in response to methyl methanesulfonate (MMS)
2020-11-18 | E-MTAB-8745 | biostudies-arrayexpress
Project description:Alkylation damage to DNA occurs when cells encounter alkylating agents in the environment or when active alkylators are generated by nitrosation of amino acids in metabolic pathways. To cope with DNA alkylation damage, cells have evolved genes that encode proteins with alkylation-specific DNA repair activities. It is notable that these repair systems are conserved from bacteria to humans. In Escherichia coli, cells exposed to a low concentration of an alkylating agent, such as N-methyl-Nâ-nitro-N-nitrosoguanidine (MNNG) or methyl methanesulfonate (MMS), show a remarkable increase in resistance to both the lethal and mutagenic effects of subsequent high-level challenge treatments with the same or other alkylating agents. This increased resistance has been known as âadaptive responseâ to alkylation damage in DNA. To date, four genes have been identified as components of this response, ada, alkA, alkB and aidB. The ada gene encodes the Ada protein, which has the dual function of a transcriptional regulator for the genes involved in the adaptive response, and a methyltransferase that demethylates two methylated bases (O6meG and O4meT) and methylphosphotriesters produced by methylating agents in the sugar phosphate backbone. The differences between the wild-type and mutant strains were characterized at transcriptome levels. In addition, the global changes in gene expressions in response to alkylating agents (MMS), in E. coli K-12 W3110 and ada mutant strains were also analyzed. The analysis of time- and strain-dependent adaptive responses revealed the regulatory and physiological characteristics of the Ada-dependent adaptive response in E. coli. In order to examine the intracellular changes that are induced by the ada gene deletion in the MMS-untreated, normal growth condition, the expression levels of genes of ada mutant cells were compared with those of wild-type cells at the mid-log growth phase (at 0.5 h sampling point). Cells were cultivated at 37oC and 250 rpm in 100 mL of Luria-Bertani (LB) medium (10 g/L tryptone, 5 g/L yeast extract, and 5 g/L NaCl) in 250-mL Erlenmeyer flasks. Transcriptome analysis were also performed for the samples (E. coli wildtype and ada mutant strains) taken at 0.5, 1.5 and 3.9 h following MMS treatment for both MMS-treated and -untreated control cultures, and the expression levels were compared.
2010-09-09 | E-GEOD-16565 | biostudies-arrayexpress
Project description:Alkylation damage to DNA occurs when cells encounter alkylating agents in the environment or when active alkylators are generated by nitrosation of amino acids in metabolic pathways. To cope with DNA alkylation damage, cells have evolved genes that encode proteins with alkylation-specific DNA repair activities. It is notable that these repair systems are conserved from bacteria to humans. In Escherichia coli, cells exposed to a low concentration of an alkylating agent, such as N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) or methyl methanesulfonate (MMS), show a remarkable increase in resistance to both the lethal and mutagenic effects of subsequent high-level challenge treatments with the same or other alkylating agents. This increased resistance has been known as “adaptive response” to alkylation damage in DNA. To date, four genes have been identified as components of this response, ada, alkA, alkB and aidB. The ada gene encodes the Ada protein, which has the dual function of a transcriptional regulator for the genes involved in the adaptive response, and a methyltransferase that demethylates two methylated bases (O6meG and O4meT) and methylphosphotriesters produced by methylating agents in the sugar phosphate backbone. The differences between the wild-type and mutant strains were characterized at transcriptome levels. In addition, the global changes in gene expressions in response to alkylating agents (MMS), in E. coli K-12 W3110 and ada mutant strains were also analyzed. The analysis of time- and strain-dependent adaptive responses revealed the regulatory and physiological characteristics of the Ada-dependent adaptive response in E. coli.
2009-08-25 | GSE16565 | GEO
Project description:Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.
2017-02-14 | GSE57789 | GEO
Project description:Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.
2017-02-14 | GSE57788 | GEO
Project description:Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.
2020-05-06 | GSE57161 | GEO