Genomic characterization of cisplatin response uncovers priming of cispla-tin-induced genes in a resistant cell line
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE173201 | GEO | 2021/06/07
REPOSITORIES: GEO
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Project description:We developed a method for genome-wide mapping of DNA excision repair named XR-seq (eXcision Repair-seq). Human nucleotide excision repair generates two incisions surrounding the site of damage, creating a ~30-mer. In XR-seq, this fragment is isolated and subjected to high-throughput sequencing. We used XR-seq to produce stranded, nucleotide-resolution maps of repair of two UV-induced DNA damages in human cells, cyclobutane pyrimidine dimers (CPDs) and (6-4) pyrimidine-pyrimidone photoproducts ((6-4)PPs). In wild-type cells, CPD repair was highly associated with transcription, specifically with the template strand. Experiments in cells defective in either transcription-coupled excision repair or general excision repair isolated the contribution of each pathway to the overall repair pattern, and showed that transcription-coupled repair of both photoproducts occurs exclusively on the template strand. XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bi-directional eRNA production at enhancers. XR-seq data also uncovered the repair characteristics and novel sequence preferences of CPDs and (6-4)PPs. XR-seq and the resulting repair maps will facilitate studies of the effects of genomic location, chromatin context, transcription, and replication on DNA repair in human cells. We have performed XR-seq for two types of UV-induced damages (CPD and (6-4)PP) in three different cell lines: NHF1, XP-C (XP4PA-SV-EB, GM15983)), and CS-B (CS1ANps3g2, GM16095). Two biological replicates were performed for each experiment, in which independent cell populations were UV treated and subjected to XR-seq.
2015-04-19 | E-GEOD-67941 | biostudies-arrayexpress
Project description:Platinum-based drug cisplatin is a widely used first-line therapy for several cancers. Cisplatin interacts with DNA mainly in the form of Pt-d(GpG) di-adduct, which stalls cell proliferation and activates DNA damage response pathway. Cisplatin DNA-adducts are primarily repaired by nucleotide excision repair system. Despite cisplatin shows a broad spectrum of anticancer activity, it has limitation of use due to acquired drug resistance and toxicity to nontargeted tissues. By integrating genome-wide high-throughput “damage-seq”, “XR-seq”, mRNA-seq approaches along with epigenomic data we studied the mechanism of action of cisplatin across the mouse genome in kidney, liver, lung and spleen. Genome-wide damage-seq data reveal that kidney is highest cisplatin-damage accumulation site, while spleen is lowest. Excision repair on transcribed strand (TS) and non-transcribed strand (NTS) in active genes is in positive correlation with gene transcription, and regarding to nucleotide excision repair efficiency, there is no significant difference across organs. Lastly, in response to cisplatin treatment ATM signaling is upregulated in kidney, liver and lung, while PKA signaling is downregulated across all organs. The methodology and data we presented here include four different mouse organs and three “omics” data, it unbiasedly constitutes a foundation for understanding the mechanism of cellular respond to cisplatin and by means of improving chemotherapy while reducing side effect to normal tissues.
2019-01-01 | GSE117167 | GEO
Project description:To determine the signaling networks that are dysregulated in platinum-resistant ovarian cancer, gene expression data were obtained from, and compared between, the ovarian cancer cell line, A2780, and its cisplatin-resistant derivative, A2780cis. Gene expression data from a cisplatin-sensitive ovarian cancer cell line (A2780) were collected and compared to gene expression data from a cisplatin-resistant cell line (A2780cis). 6 independent experiments were completed for both the sensitive and resistant cell lines.
2011-11-05 | E-GEOD-33482 | biostudies-arrayexpress
Project description:We report the application of single-molecule-based sequencing technology (XR-seq) for high-throughput profiling of nucleotide excision repair in Drosophila four developmental stages and S2 cells. By obtaining over six billion bases of sequence from UV and cisplatin damage antibodies immunoprecipitated excision DNA, we generated genome-wide nucleotide excision repair maps of Drosophila Embryo, Larva, Pupa , two gender of adults and S2 cells . We find that Drosophila performs transcription-coupled repair (TCR) at all its developmental stages. S2 cell carry out TCR response to both UV and Cisplatin damage. Finally, we show that XPC repair factor is required for both global and transcription-coupled repair in Drosophila. This study provides the mechanism of nucleotide excision repair of Drosophila in vivo and vitro response to UV and Cisplatin damage.
2022-02-25 | GSE184926 | GEO
Project description:To determine the signaling networks that are dysregulated in platinum-resistant ovarian cancer, gene expression data were obtained from, and compared between, the ovarian cancer cell line, A2780, and its cisplatin-resistant derivative, A2780cis.
2011-11-05 | GSE33482 | GEO
Project description:We developed a method for genome-wide mapping of DNA excision repair named XR-seq (eXcision Repair-seq). Human nucleotide excision repair generates two incisions surrounding the site of damage, creating a ~30-mer. In XR-seq, this fragment is isolated and subjected to high-throughput sequencing. We used XR-seq to produce stranded, nucleotide-resolution maps of repair of two UV-induced DNA damages in human cells, cyclobutane pyrimidine dimers (CPDs) and (6-4) pyrimidine-pyrimidone photoproducts ((6-4)PPs). In wild-type cells, CPD repair was highly associated with transcription, specifically with the template strand. Experiments in cells defective in either transcription-coupled excision repair or general excision repair isolated the contribution of each pathway to the overall repair pattern, and showed that transcription-coupled repair of both photoproducts occurs exclusively on the template strand. XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bi-directional eRNA production at enhancers. XR-seq data also uncovered the repair characteristics and novel sequence preferences of CPDs and (6-4)PPs. XR-seq and the resulting repair maps will facilitate studies of the effects of genomic location, chromatin context, transcription, and replication on DNA repair in human cells.
2015-04-19 | GSE67941 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE15372: Expression data from A2780 (cisplatin-sensitive) and Round5 A2780 (cisplatin-resistant) cell lines. GSE15373: Promoter CpG island methylation data from A2780 (cisplatin-sensitive) and Round5 A2780 (cisplatin-resistant) cell lines. Refer to individual Series
2009-04-17 | E-GEOD-15709 | biostudies-arrayexpress
Project description:The goal of this study was to determine genes with altered expression after selection of ovarian cancer cells for survival in increasing concentrations of cisplatin. A series of progressively cispatin resistant derivatives of A2780 ovarian cancer cell lines was hybridized to spotted cDNA microarrays using two color technology using the parental A2780 cells as a reference. Duplicate hybridizations were carried out for each resistant derivative.
2013-12-22 | E-GEOD-44022 | biostudies-arrayexpress
Project description:Cisplatin is the most commonly used chemotherapeutic drug for treating solid tumors. However, its toxicity and the innate or acquired resistance of cancer cells to the drug limit its usefulness. Cisplatin kills cells by forming cisplatin-DNA adducts, most commonly in the form of Pt-d(GpG) diadduct. We recently showed that repair of this adduct within 2 hours following injection is controlled by two circadian programs: (1) The circadian clock controls transcription of 2000 genes in mouse liver and thereby controls repair of the transcribed strand of these genes via transcription coupled repair in a rhythmic fashion unique to each gene’s phase of transcription. (2) The basal excision repair activity itself is controlled by the circadian clock with a single phase at which the repair of the non-transcribed strand and the rest of the genome take place. Here, we have followed the repair kinetic for long periods genome-wide both globally and at single nucleotide resolution by the Excision Repair-sequencing (XR-seq) method to gain further insight into cisplatin DNA damage and repair with the aim of improving the therapeutic index of the drug. Our data show that transcription-driven repair is complete after two days, while completion of basal repair of nontranscribed strands, silent genes and intergenic regions requires weeks. In rhythmically controlled genes, oscillations of transcribed repair are observed up to 2 days post-injection, and in both constitutively transcribed and rhythmic genes, we see a trend in template strand repair with time from the 5’to 3’ end. These findings add to the complexity of circadian- and transcription-dependent and -independent control of repair exhibited by this model organism in response to cisplatin.
2019-06-24 | GSE132002 | GEO
Project description:Cisplatin is the most commonly used chemotherapeutic drug for treating solid tumors. However, its toxicity and the innate or acquired resistance of cancer cells to the drug limit its usefulness. Cisplatin kills cells by forming cisplatin-DNA adducts, most commonly in the form of Pt-d(GpG) diadduct. We recently showed that repair of this adduct within 2 hours following injection is controlled by two circadian programs: (1) The circadian clock controls transcription of 2000 genes in mouse liver and thereby controls repair of the transcribed strand of these genes via transcription coupled repair in a rhythmic fashion unique to each gene’s phase of transcription. (2) The basal excision repair activity itself is controlled by the circadian clock with a single phase at which the repair of the non-transcribed strand and the rest of the genome take place. Here, we have followed the repair kinetic for long periods genome-wide both globally and at single nucleotide resolution by the Excision Repair-sequencing (XR-seq) method to gain further insight into cisplatin DNA damage and repair with the aim of improving the therapeutic index of the drug. Our data show that transcription-driven repair is complete after two days, while completion of basal repair of nontranscribed strands, silent genes and intergenic regions requires weeks. In rhythmically controlled genes, oscillations of transcribed repair are observed up to 2 days post-injection, and in both constitutively transcribed and rhythmic genes, we see a trend in template strand repair with time from the 5’to 3’ end. These findings add to the complexity of circadian- and transcription-dependent and -independent control of repair exhibited by this model organism in response to cisplatin.
2019-06-24 | GSE132993 | GEO