G-quadruplex on Chromosomal DNA Negatively Regulates Topoisomerase 1 Activity
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PROVIDER: PRJNA1000576 | ENA |
REPOSITORIES: ENA
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Project description:Human DNA topoisomerase 1 (Top1) is a crucial enzyme responsible for alleviating torsional stress on DNA during transcription and replication, thereby maintaining genome stability. Previous researches had found that non-working Top1 interacted extensively with chromosomal DNA in human cells. However, the reason for its retention on chromosomal DNA remained unclear. In this study, we discovered a close association between Top1 and chromosomal DNA, specifically linked to the presence of G-quadruplex (G4) structures. G4 structures, formed during transcription, trap Top1 and hinder its ability to relax neighboring DNAs. Disruption of the Top1-G4 interaction using G4 ligand relieved the inhibitory effect of G4 on Top1 activity, resulting in a further reduction of R-loop levels in cells. Additionally, the activation of Top1 through the use of a G4 ligand enhanced the toxicity of Top1 inhibitors towards cancer cells. Our study uncovers a negative regulation mechanism of human Top1 and highlights a novel pathway for activating Top1.
2024-01-01 | GSE239692 | GEO
Project description:Human DNA topoisomerase 1 (Top1) is a crucial enzyme responsible for alleviating torsional stress on DNA during transcription and replication, thereby maintaining genome stability. Previous researches had found that non-working Top1 interacted extensively with chromosomal DNA in human cells. However, the reason for its retention on chromosomal DNA remained unclear. In this study, we discovered a close association between Top1 and chromosomal DNA, specifically linked to the presence of G-quadruplex (G4) structures. G4 structures, formed during transcription, trap Top1 and hinder its ability to relax neighboring DNAs. Disruption of the Top1-G4 interaction using G4 ligand relieved the inhibitory effect of G4 on Top1 activity, resulting in a further reduction of R-loop levels in cells. Additionally, the activation of Top1 through the use of a G4 ligand enhanced the toxicity of Top1 inhibitors towards cancer cells. Our study uncovers a negative regulation mechanism of human Top1 and highlights a novel pathway for activating Top1.
2024-01-01 | GSE239690 | GEO
Project description:G-quadruplex on Chromosomal DNA Negatively Regulates Topoisomerase 1 Activity
| PRJNA987185 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-01-01 | GSE239694 | GEO
Project description: Not available
| S-EPMC10954455 | biostudies-literature
Project description:Eukaryotic topoisomerase I and II relax DNA and are key components in the processes of DNA replication, transcription and genome stability. It is not clear, however, how their activity controls epigenetic states across an entire eukaryotic genome. Using the fission yeast model Schizosaccharomyces pombe, we investigate genome-wide how topoisomerases affect chromatin formation through nucleosome occupancy and regulate transcription. We show that topoisomerase activity is required for nucleosome turnover at promoter regions, affecting epigenetic gene regulatory states, and for effective termination of transcription.
2010-07-02 | E-MEXP-1850 | biostudies-arrayexpress
Project description:Trovafloxacin is a broad spectrum antibiotic that inhibits the uncoiling of supercoiled DNA in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. Specific members of this drug family display high activity against eukaryotic type II topoisomerase, as well as cultured mammalian cells and in vivo tumor models. Trovafloxacin seems to have a higher affinity for eukaryotic polymerase II system than the other quinolone agents tested. This effect coupled with other factors, such as an inflammatory response, might result in a hepatotoxic reaction seen with drug. In this study we found genes regulated by trovafloxacin - induced and repressed - to be located much closer to each other than genes distributed randomly all over the genome (< 100 kbp). Keywords: Trovafloxacin-treated human hepatocytes versus non-treated human hepatocytes
2008-10-01 | GSE11941 | GEO
Project description:Analysis of topoisomerase function in bacterial replication fork movement: use of DNA microarrays. We used DNA microarrays of the Escherichia coli genome to trace the progression of chromosomal replication forks in synchronized cells. We found that both DNA gyrase and topoisomerase IV (topo IV) promote replication fork progression. When both enzymes were inhibited, the replication fork stopped rapidly. The elongation rate with topo IV alone was 1/3 of normal. Genetic data confirmed and extended these results. Inactivation of gyrase alone caused a slow stop of replication. Topo IV activity was sufficient to prevent accumulation of (+) supercoils in plasmid DNA in vivo, suggesting that topo IV can promote replication by removing (+) supercoils in front of the chromosomal fork. This study is detailed in Khodursky AB et al.(2000) Proc Natl Acad Sci U S A 97:9419-24 Keywords: other
2001-07-30 | E-GEOD-8 | biostudies-arrayexpress
Project description:The G-quadruplex is an alternative DNA structural motif that is considered to be functionally important in the mammalian genome. Herein, we address the hypothesis that G-quadruplex structures can exist within double-stranded genomic DNA using a G-quadruplex-specific probe. An engineered antibody is employed to enrich for DNA containing G-quadruplex structures, followed by deep sequencing to detect and map G-quadruplexes at high resolution in genomic DNA from human breast adenocarcinoma cells. Our high sensitivity structure-based pull-down strategy enables the isolation of genomic DNA fragments bearing a single as well as multiple G-quadruplex structures. Stable G-quadruplex structures are found in sub-telomeres, gene bodies and gene regulatory regions. For a sample of identified target genes, we show that G-quadruplex stabilizing ligands can modulate transcription. These results confirm the existence of G-quadruplex structures and their persistence in human genomic DNA. Four independent libraries have been enriched in DNA G-quadruplex structures using a G-quadruplex-specific probe. One genomic input library was sequenced as control. Deep-sequencing of these libraries allowed the mapping of G-quadruplexes on the genome.
2013-05-08 | E-GEOD-45241 | biostudies-arrayexpress
Project description:Analysis of topoisomerase function in bacterial replication fork movement: use of DNA microarrays. We used DNA microarrays of the Escherichia coli genome to trace the progression of chromosomal replication forks in synchronized cells. We found that both DNA gyrase and topoisomerase IV (topo IV) promote replication fork progression. When both enzymes were inhibited, the replication fork stopped rapidly. The elongation rate with topo IV alone was 1/3 of normal. Genetic data confirmed and extended these results. Inactivation of gyrase alone caused a slow stop of replication. Topo IV activity was sufficient to prevent accumulation of (+) supercoils in plasmid DNA in vivo, suggesting that topo IV can promote replication by removing (+) supercoils in front of the chromosomal fork. This study is detailed in Khodursky AB et al.(2000) Proc Natl Acad Sci U S A 97:9419-24 Keywords: other
2001-07-30 | GSE8 | GEO