scholarly journals DNA Topoisomerase 2-Alpha

2020 ◽  
Author(s):  
Keyword(s):  
Dna Topoisomerase ◽  
Topoisomerase 2 ◽  
Topoisomerase 2 Alpha

scholarly journals Profiling of Biomarkers for the Exposure of Polycyclic Aromatic Hydrocarbons: Lamin-A/C Isoform 3, Poly[ADP-ribose] Polymerase 1, and Mitochondria Copy Number Are Identified as Universal Biomarkers

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Hwan-Young Kim ◽  
Hye-Ran Kim ◽  
Min-Gu Kang ◽  
Nguyen Thi Dai Trang ◽  
Hee-Jo Baek ◽  
...  
Keyword(s):  
Cell Lines ◽  
Copy Number ◽  
Lamin A ◽  
Annexin A1 ◽  
Mtdna Copy Number ◽  
Dna Topoisomerase ◽  
Polycyclic Aromatic ◽  
Topoisomerase 2 ◽  
Topoisomerase 2 Alpha ◽  
Parp 1

This study investigated the profiling of polycyclic aromatic hydrocarbon- (PAH-) induced genotoxicity in cell lines and zebrafish. Each type of cells displayed different proportionality of apoptosis. Mitochondrial DNA (mtDNA) copy number was dramatically elevated after 5-day treatment of fluoranthene and pyrene. The notable deregulated proteins for PAHs exposure were displayed as follows: lamin-A/C isoform 3 and annexin A1 for benzopyrene; lamin-A/C isoform 3 and DNA topoisomerase 2-alpha for pentacene; poly[ADP-ribose] polymerase 1 (PARP-1) for fluoranthene; and talin-1 and DNA topoisomerase 2-alpha for pyrene. Among them, lamin-A/C isoform 3 and PARP-1 were further confirmed using mRNA and protein expression study. Obvious morphological abnormalities including curved backbone and cardiomegaly in zebrafish were observed in the 54 hpf with more than 400 nM of benzopyrene. In conclusion, the change of mitochondrial genome (increased mtDNA copy number) was closely associated with PAH exposure in cell lines and mesenchymal stem cells. Lamin-A/C isoform 3, talin-1, and annexin A1 were identified as universal biomarkers for PAHs exposure. Zebrafish, specifically at embryo stage, showed suitablein vivomodel for monitoring PAHs exposure to hematopoietic tissue and other organs.

Co-expression of cancer testis antigens and topoisomerase 2-alpha in triple negative breast carcinomas

2014 ◽  
Vol 116 (5) ◽  
pp. 740-746 ◽  
Author(s):  
Ivana Mrklić ◽  
Giulio Cesare Spagnoli ◽  
Antonio Juretić ◽  
Zenon Pogorelić ◽  
Snježana Tomić
Keyword(s):  
Triple Negative ◽  
Breast Carcinomas ◽  
Cancer Testis Antigens ◽  
Topoisomerase 2 ◽  
Topoisomerase 2 Alpha ◽  
Cancer Testis

Protein Profiling of Hematopoietic Progenitor Cells and Leukemia Cells Identifies Novel Biomarkers Associated with Exposure of Polycyclic Aromatic Hydrocarbons

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4690-4690
Author(s):  
Hwan-Young Kim ◽  
Hye-Ran Kim ◽  
Stephanie J. Won ◽  
Hee-Jo Baek ◽  
Jae-Dong Moon ◽  
...  
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Cell Count ◽  
Cell Lines ◽  
Aromatic Hydrocarbons ◽  
Leukemia Cell ◽  
Control Group ◽  
Leukemia Cell Lines ◽  
Polycyclic Aromatic ◽  
Topoisomerase 2 ◽  
Topoisomerase 2 Alpha

Abstract Abstract 4690 Background: Polycyclic aromatic hydrocarbons (PAHs) are one of the major environmental hazardous compounds in living environment generated by combustion of fossil fuels. PAHs are classified as carcinogens by International Agency for Research on Cancer. However, the study on biomarkers and biological effect of PAHs has not been thoroughly studied in peripheral blood stem cells (PBSC) and leukemia cell lines. Therefore, the present study investigated biological characteristics and biomarkers in hematopoietic cells and leukemia cell lines after exposure of PAHs. Materials and Methods: Cytokine stimulation (10 mg/kg/d) was used in a 28-year-old healthy male donor from 5 d before to 2 d after. One to three apheresis procedures were planned for on day 0, day 1, and day 2, using a Baxter CS-3000 PLUS machine (Baxter Healthcare) and a COBE-Spectra (Gambro). PBSC and three leukemia cell lines (THP-1, Molt-4 and K562) were cultured in RPMI media containing 10% fetal bovine serum. In this study, four types of PAHs- Benzopyrene (BaP), Pentacene, Fluoranthene and Pyrene -were added in the cell culture media with 100μM concentration (Sigma-Aldrich, USA). Cell count was performed using an automated blood cell analyzer. Viability and apoptosis were assessed by trypan blue dye exclusion test and flowcytometry based on annexin V staining protocol. Cytotoxicity was determined by the water-soluble tetrazolium salts -1 assay. Proteomics in mitochondrial-rich cytoplasmic fraction was performed using nano-LC-ESI-MS/MS analysis. The acquired fragment spectra were searched in the BioWorksBrowser (version Rev. 3.3.1 SP1, Thermo Fisher Scientific Inc., CA) with the SEQUEST search engines against National Center for Biotechnology Information (http://www.ncbi.nlm.nih. gov/) non-redundant human database. Results: Depending on the type of PAHs, each cell count showed different aspects. In comparison to control group, Fluoranthene displayed profound significant reduction in cell count, especially in PBSC and THP-1 cells. Viability decreased significantly after two days of exposuring into Fluoranthene. On the third day of PAHs exposure, viability reduced remarkably in all the cells. Each type of cell lines displayed different proportionality of apoptosis. Several hundreds of PAHs exposure biomarkers were identified in comparison to control group. The notable biomarkers for PAHs exposure were displayed as following: prelamin-A/C isoform 3 and annexin A1 for BaP; prelamin-A/C isoform 3 and DNA topoisomerase 2-alpha for Pentacene; poly [ADP-ribose] polymerase 1 for Fluoranthene; talin-1 and DNA topoisomerase 2-alpha for Pyrene. By using Gene Ontology tool, we further identified protein candidate biomarkers for PAH exposure. Conclusion: This study shows new biomarkers and biological characteristics of polycyclic aromatic hydrocarbons exposure in hematopoietic tissue. Specifically, talin-1 was identified as universal biomarker for PAHs exposure. Disclosures: No relevant conflicts of interest to declare.

Topoisomerase 2 alpha: a real predictor of anthracycline efficacy?

2012 ◽  
Vol 14 (3) ◽  
pp. 163-168 ◽  
Author(s):  
Atocha Romero ◽  
Trinidad Caldés ◽  
Eduardo Díaz-Rubio ◽  
Miguel Martín
Keyword(s):  
Topoisomerase 2 ◽  
Topoisomerase 2 Alpha

scholarly journals Transcription-associated topoisomerase activities control DNA-breaks production by G-quadruplex ligands

2020 ◽  
Author(s):  
A. Pipier ◽  
M. Bossaert ◽  
J.F. Riou ◽  
C. Noirot ◽  
L-T. Nguyễn ◽  
...  
Keyword(s):  
Point Mutations ◽  
Telomere Maintenance ◽  
Cross Resistance ◽  
Cell Cytotoxicity ◽  
Dna Breaks ◽  
Topoisomerase 1 ◽  
G Quadruplex ◽  
Topoisomerase 2 ◽  
Topoisomerase 2 Alpha ◽  
Almost All

AbstractG-quadruplexes (G4), non-canonical DNA structures, are involved in several essential processes. Stabilization of G4 structures by small compounds (G4 ligands) affects almost all DNA transactions, including telomere maintenance and genomic stability. Here, thanks to a powerful and unbiased genetic approach, we identify topoisomerase 2-alpha (TOP2A) as the main effector of cell cytotoxicity induced by CX5461, a G4 ligand currently undergoing phase I/II clinical trials. This approach also allowed to identify new point mutations affecting TOP2A activity without compromising cell viability. Moreover, based on cross-resistance studies and siRNA-based protein depletion we report that TOP2A plays a major role in cell cytotoxicity induced by two unrelated clastogenic G4 ligands, CX5461 and pyridostatin (PDS). We also report that cytotoxic effects induced by both compounds are associated with topoisomerase 2-mediated DNA breaks production. Finally, we show that TOP2-mediated DNA breaks production is strongly associated with RNA Pol II-dependent transcription and is countered by topoisomerase 1 (TOP1). Altogether our results indicate that clastogenic G4 ligands act as DNA structure-driven TOP2-poisons at transcribed regions bearing G-quadruplex structures.

scholarly journals Canonical non-homologous end-joining promotes genome mutagenesis and translocations induced by transcription-associated DNA topoisomerase 2 activity

2020 ◽  
Vol 48 (16) ◽  
pp. 9147-9160
Author(s):  
Joaquín Olmedo-Pelayo ◽  
Diana Rubio-Contreras ◽  
Fernando Gómez-Herreros
Keyword(s):  
Cell Death ◽  
Topoisomerase Ii ◽  
Genome Instability ◽  
Metabolic Enzyme ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Dna Topoisomerase ◽  
Transient Complex ◽  
Topoisomerase 2 ◽  
Non Homologous End Joining

Abstract DNA topoisomerase II (TOP2) is a major DNA metabolic enzyme, with important roles in replication, transcription, chromosome segregation and spatial organisation of the genome. TOP2 is the target of a class of anticancer drugs that poison the DNA-TOP2 transient complex to generate TOP2-linked DNA double-strand breaks (DSBs). The accumulation of DSBs kills tumour cells but can also result in genome instability. The way in which topoisomerase activity contributes to transcription remains unclear. In this work we have investigated how transcription contributes to TOP2-dependent DSB formation, genome instability and cell death. Our results demonstrate that gene transcription is an important source of abortive TOP2 activity. However, transcription does not contribute significantly to apoptosis or cell death promoted by TOP2-induced DSBs. On the contrary: transcription-dependent breaks greatly contribute to deleterious mutations and translocations, and can promote oncogenic rearrangements. Importantly, we show that TOP2-induced genome instability is mediated by mutagenic canonical non-homologous end joining whereas homologous recombination protects cells against these insults. Collectively, these results uncover mechanisms behind deleterious effects of TOP2 abortive activity during transcription, with relevant implications for chemotherapy.

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