Increased DNA topoisomerase I activity in aging human cell chromatin

1984 ◽  
Vol 4 (10) ◽  
pp. 861-868 ◽  
Author(s):  
Claude Hamelin ◽  
Lise Cousineau ◽  
Michel Dion ◽  
Jocelyn Yelle
Keyword(s):  
Topoisomerase I ◽  
Dna Unwinding ◽  
Type I ◽  
Dna Topoisomerase I ◽  
Dna Topoisomerase ◽  
Human Diploid Fibroblasts ◽  
In Vitro Aging ◽  
Age Related ◽  
Cell Age

Chromatin-associated DNA topoisomerase I activity was measured in human diploid fibroblasts during in vitro aging. No diilerence was detected as a function of cell age in the nicking and the closing activities of the DNA-unwinding enzyme. The capacity of type-I topoisomerase to relax superhelical DNA molecules was, however, increased in aged cells. An age-related increase in nucleoprotein content was also observed.

scholarly journals Flavonoids in Helichrysum pamphylicum Inhibit Mammalian Type I DNA Topoisomerase

2008 ◽  
Vol 63 (1-2) ◽  
pp. 69-74 ◽  
Author(s):  
Zeki Topcu ◽  
Bintug Ozturk ◽  
Ozlem Kucukoglu ◽  
Emrah Kilinc
Keyword(s):  
Antioxidant Capacity ◽  
Topoisomerase I ◽  
Type I ◽  
Dna Topoisomerase I ◽  
Dependent Manner ◽  
Dna Topoisomerase ◽  
Total Antioxidant ◽  
Supercoil Relaxation ◽  
Dose Dependent

DNA topoisomerases are important targets for cancer chemotherapy. We investigated the effects of a methanolic extract of Helichrysum pamphylicum on mammalian DNA topoisomerase I via in vitro plasmid supercoil relaxation assays. The extracts manifested a considerable inhibition of the enzyme’s activity in a dose-dependent manner. We also performed a HPLC analysis to identify the flavonoid content of the H. pamphylicum extract and tested the identified flavonoids; luteolin, luteolin-4-glucoside, naringenin, helichrysinA and isoquercitrin, on DNA topoisomerase I activity. The measurement of the total antioxidant capacity of the flavonoid standards suggested that the topoisomerase inhibition might be correlated with the antioxidant capacity of the plant.

scholarly journals Genome-wide proximity between RNA polymerase and DNA topoisomerase I supports transcription in Streptococcus pneumoniae

PLoS Genetics ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. e1009542
Author(s):  
María-José Ferrándiz ◽  
Pablo Hernández ◽  
Adela G. de la Campa
Keyword(s):  
Streptococcus Pneumoniae ◽  
Rna Polymerase ◽  
Topoisomerase I ◽  
Type I ◽  
Dna Topoisomerase I ◽  
Sequence Motifs ◽  
Dna Topoisomerase ◽  
Genome Wide

Streptococcus pneumoniae is a major cause of disease and death that develops resistance to multiple antibiotics. DNA topoisomerase I (TopoI) is a novel pneumococcal drug target. TopoI is the sole type-I pneumococcal topoisomerase that regulates supercoiling homeostasis in this bacterium. In this study, a direct in vitro interaction between TopoI and RNA polymerase (RNAP) was detected by surface plasmon resonance. To understand the interplay between transcription and supercoiling regulation in vivo, genome-wide association of RNAP and TopoI was studied by ChIP-Seq. RNAP and TopoI were enriched at the promoters of 435 and 356 genes, respectively. Higher levels of expression were consistently measured in those genes whose promoters recruit both RNAP and TopoI, in contrast with those enriched in only one of them. Both enzymes occupied a narrow region close to the ATG codon. In addition, RNAP displayed a regular distribution throughout the coding regions. Likewise, the summits of peaks called with MACS tool, mapped around the ATG codon in both cases. However, RNAP showed a broader distribution towards ATG-downstream positions. Remarkably, inhibition of RNAP with rifampicin prevented the localization of TopoI at promoters and, vice versa, inhibition of TopoI with seconeolitsine prevented the binding of RNAP to promoters. This indicates a functional interplay between RNAP and TopoI. To determine the molecular factors responsible for RNAP and TopoI co-recruitment, we looked for DNA sequence motifs. We identified a motif corresponding to a -10-extended promoter for TopoI and for RNAP. Furthermore, RNAP was preferentially recruited to genes co-directionally oriented with replication, while TopoI was more abundant in head-on genes. TopoI was located in the intergenic regions of divergent genes pairs, near the promoter of the head-on gene of the pair. These results suggest a role for TopoI in the formation/stability of the RNAP-DNA complex at the promoter and during transcript elongation.

Minor groove dimeric bisbenzimidazoles inhibit in vitro DNA binding to eukaryotic DNA topoisomerase I

2010 ◽  
Vol 75 (6) ◽  
pp. 695-701 ◽  
Author(s):  
O. Yu. Susova ◽  
A. A. Ivanov ◽  
S. S. Morales Ruiz ◽  
E. A. Lesovaya ◽  
A. V. Gromyko ◽  
...  
Keyword(s):  
Dna Binding ◽  
Topoisomerase I ◽  
Minor Groove ◽  
Dna Topoisomerase I ◽  
Dna Topoisomerase ◽  
Dimeric Bisbenzimidazoles ◽  
Eukaryotic Dna

Synthesis, crystal structure, DNA interaction and in vitro anticancer activity of a Cu(ii) complex of purpurin: dual poison for human DNA topoisomerase I and II

RSC Advances ◽  
2014 ◽  
Vol 4 (103) ◽  
pp. 59344-59357 ◽  
Author(s):  
Piyal Das ◽  
Chetan Kumar Jain ◽  
Sanjoy K. Dey ◽  
Rajat Saha ◽  
Abhishek Dutta Chowdhury ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Topoisomerase I ◽  
Dna Interaction ◽  
Dna Topoisomerase I ◽  
Oxygen Species ◽  
Dna Topoisomerase ◽  
Human Dna ◽  
Anti Tumor Activity ◽  
Human Dna Topoisomerase I

Although generation of reactive oxygen species (ROS) by anthracycline anticancer drugs is essential for anti-tumor activity, they make these drugs cardiotoxic.

scholarly journals Nucleosomes represent a physical barrier for cleavage activity of DNA topoisomerase I in vivo

2008 ◽  
Vol 409 (3) ◽  
pp. 651-656 ◽  
Author(s):  
Francesca Di Felice ◽  
Francesco Chiani ◽  
Giorgio Camilloni
Keyword(s):  
Topoisomerase I ◽  
Basic Question ◽  
Dna Topoisomerase I ◽  
Physical Barrier ◽  
Dna Topoisomerase ◽  
Histone Octamer ◽  
Cleavage Activity ◽  
Cellular Dna

DNA topoisomerase I together with the other cellular DNA topoisomerases releases the torsional stress from DNA caused by processes such as replication, transcription and recombination. Despite the well-defined knowledge of its mechanism of action, DNA topoisomerase I in vivo activity has been only partially characterized. In fact the basic question concerning the capability of the enzyme to cleave and rejoin DNA wrapped around a histone octamer remains still unanswered. By studying both in vivo and in vitro the cleavage activity of DNA topoisomerase I in the presence of camptothecin on a repeated trinucleotide sequence, (TTA)35, lying in chromosome XIII of Saccharomyces cerevisiae, we can conclude that nucleosomes represent a physical barrier for the enzyme activity.

scholarly journals 1H-Benzimidazole derivatives as mammalian DNA topoisomerase I inhibitors.

2007 ◽  
Vol 54 (3) ◽  
pp. 561-565 ◽  
Author(s):  
A Selcen Alpan ◽  
H Semih Gunes ◽  
Zeki Topcu
Keyword(s):  
Topoisomerase I ◽  
Biological Properties ◽  
Benzimidazole Derivatives ◽  
Type I ◽  
Mass Spectral Data ◽  
Dna Topoisomerase ◽  
Mass Spectral ◽  
Elemental Analyses ◽  
Supercoil Relaxation

Benzimidazole is one of the most important heterocyclic groups manifesting various biological properties, such as antibacterial, antifungal, antimicrobial, antiprotozoal and antihelmintic activities. Several benzimidazole derivatives are also active as inhibitors of type I DNA topoisomerases. In this study, three 1H-benzimidazole derivatives with different electronic characteristics at position 5-, namely 5-chloro-4-(1H-benzimidazole-2-yl)phenol (Cpd I), 5-methyl-4-(1H-benzimidazole-2-yl)phenol (Cpd II) and 4-(1H-benzimidazole-2-yl)phenol (Cpd III), were synthesized and evaluated for their effects on mammalian type I DNA topoisomerase activity using quantitative in vitro plasmid supercoil relaxation assays. For the structure elucidation of the compounds, melting points, UV, IR, 1H NMR, 13C NMR, mass spectral data and elemental analyses were interpreted. Among the compounds, 5-methyl-4-(1H-benzimidazole-2-yl)phenol (Cpd II) manifested relatively potent topoisomerase I inhibition.

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