The Coffee Constituent Chlorogenic Acid Induces Cellular DNA Damage and Formation of Topoisomerase I– and II–DNA Complexes in Cells

2012 ◽  
Vol 60 (30) ◽  
pp. 7384-7391 ◽  
Author(s):  
Estefanía Burgos-Morón ◽  
José Manuel Calderón-Montaño ◽  
Manuel Luis Orta ◽  
Nuria Pastor ◽  
Concepción Pérez-Guerrero ◽  
...  
Keyword(s):  
Dna Damage ◽  
Chlorogenic Acid ◽  
Topoisomerase I ◽  
Dna Complexes ◽  
Cellular Dna ◽  
In Cells

Alpha, beta-unsaturated lactones 2-furanone and 2-pyrone induce cellular DNA damage, formation of topoisomerase I- and II-DNA complexes and cancer cell death

2013 ◽  
Vol 222 (1) ◽  
pp. 64-71 ◽  
Author(s):  
José Manuel Calderón-Montaño ◽  
Estefanía Burgos-Morón ◽  
Manuel Luis Orta ◽  
Nuria Pastor ◽  
Caroline A. Austin ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Cancer Cell ◽  
Topoisomerase I ◽  
Dna Complexes ◽  
Cancer Cell Death ◽  
Alpha Beta ◽  
Unsaturated Lactones ◽  
Cellular Dna

scholarly journals Structural and functional interactions of the prostate cancer suppressor protein NKX3.1 with topoisomerase I

2013 ◽  
Vol 453 (1) ◽  
pp. 125-136 ◽  
Author(s):  
Liang-Nian Song ◽  
Cai Bowen ◽  
Edward P. Gelmann
Keyword(s):  
Dna Damage ◽  
Protein Interactions ◽  
Topoisomerase I ◽  
Cellular Response ◽  
Peptide Fragments ◽  
The Core ◽  
Tumour Suppressor Protein ◽  
Linker Domain ◽  
In Cells

NKX3.1 (NK3 homeobox 1) is a prostate tumour suppressor protein with a number of activities that are critical for its role in tumour suppression. NKX3.1 mediates the cellular response to DNA damage by interacting with ATM (ataxia telangiectasia mutated) and by activation of topoisomerase I. In the present study we characterized the interaction between NKX3.1 and topoisomerase I. The NKX3.1 homeodomain binds to a region of topoisomerase I spanning the junction between the core and linker domains. Loss of the topoisomerase I N-terminal domain, a region for frequent protein interactions, did not affect binding to NKX3.1 as was shown by the activation of Topo70 (N-terminal truncated topoisomerase I) in vitro. In contrast, NKX3.1 interacts with the enzyme reconstituted from peptide fragments of the core and linker active site domains, but inhibits the DNA-resolving activity of the reconstituted enzyme in vitro. The effect of NKX3.1 on both Topo70 and the reconstituted enzyme was seen in the presence and absence of camptothecin. Neither NKX3.1 nor CPT (camptothecin) had an effect on the interaction of the other with topoisomerase I. Therefore the interactions of NKX3.1 and CPT with the linker domain of topoisomerase I are mutually exclusive. However, in cells the effect of NKX3.1 on topoisomerase binding to DNA sensitized the cells to cellular toxicity and the induction of apoptosis by low doses of CPT. Lastly, topoisomerase I is important for the effect of NKX3.1 on cell survival after DNA damage as topoisomerase knockdown blocked the effect of NKX3.1 on clonogenicity after DNA damage. Therefore NKX3.1 and topoisomerase I interact in vitro and in cells to affect the CPT sensitivity and DNA-repair functions of NKX3.1.

Identification of a Topoisomerase I Mutant, scsA1, as an Extragenic Suppressor of a Mutation in scaANBS1, the Apparent Homolog of Human Nibrin in Aspergillus nidulans

Genetics ◽  
2003 ◽  
Vol 164 (3) ◽  
pp. 935-945 ◽  
Author(s):  
Marcia R Z Kress Fagundes ◽  
Larissa Fernandes ◽  
Marcela Savoldi ◽  
Steven D Harris ◽  
Maria H S Goldman ◽  
...  
Keyword(s):  
Dna Damage ◽  
Aspergillus Nidulans ◽  
Topoisomerase I ◽  
Cell Cycle Checkpoint ◽  
Dna Double Strand Breaks ◽  
Dna Damaging Agents ◽  
Cycle Checkpoint ◽  
Increased Sensitivity ◽  
Cellular Dna ◽  
Extragenic Suppressors

Abstract The Mre11-Rad50-Nbs1 protein complex has emerged as a central player in the human cellular DNA damage response, and recent observations suggest that these proteins are at least partially responsible for the linking of DNA damage detection to DNA repair and cell cycle checkpoint functions. Mutations in scaANBS1, which encodes the apparent homolog of human nibrin in Aspergillus nidulans, inhibit growth in the presence of the antitopoisomerase I drug camptothecin. This article describes the selection and characterization of extragenic suppressors of the scaA1 mutation, with the aim of identifying other proteins that interfere with the pathway or complex in which the ScaA would normally be involved. Fifteen extragenic suppressors of the scaA1 mutation were isolated. The topoisomerase I gene can complement one of these suppressors. Synergistic interaction between the scaANBS1 and scsATOP1 genes in the presence of DNA-damaging agents was observed. Overexpression of topoisomerase I in the scaA1 mutant causes increased sensitivity to DNA-damaging agents. The scsATOP1 and the scaANBS1 gene products could functionally interact in pathways that either monitor or repair DNA double-strand breaks.

Use of the comet assay to measure DNA damage in cells exposed to photosensitizers and gamma radiation

1999 ◽  
Vol 96 (1) ◽  
pp. 143-146 ◽  
Author(s):  
J.-P. Pouget ◽  
J.-L. Ravanat ◽  
T. Douki ◽  
M.-J. Richard ◽  
J. Cadet
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Gamma Radiation ◽  
In Cells

scholarly journals Targeting Protein-Protein Interactions in the DNA Damage Response Pathways for Cancer Chemotherapy

2021 ◽  
Author(s):  
Kerry Silva McPherson ◽  
Dmitry Korzhnev
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Protein Interactions ◽  
Cell Cycle Progression ◽  
Protein Protein Interactions ◽  
Cycle Progression ◽  
Damage Recognition ◽  
Damage Response ◽  
Cellular Dna ◽  
Dna Damage Recognition

Cellular DNA damage response (DDR) is an extensive signaling network that orchestrates DNA damage recognition, repair and avoidance, cell cycle progression and cell death. DDR alternation is a hallmark of...

scholarly journals The DNA damage inducible lncRNA SCAT7 regulates genomic integrity and topoisomerase 1 turnover in lung adenocarcinoma

NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Luisa Statello ◽  
Mohamad M Ali ◽  
Silke Reischl ◽  
Sagar Mahale ◽  
Subazini Thankaswamy Kosalai ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Cancer Biology ◽  
Topoisomerase I ◽  
Cell Cycle Checkpoints ◽  
Topoisomerase 1 ◽  
Damage Response ◽  
Promote Cell Survival

Abstract Despite the rapid improvements in unveiling the importance of lncRNAs in all aspects of cancer biology, there is still a void in mechanistic understanding of their role in the DNA damage response. Here we explored the potential role of the oncogenic lncRNA SCAT7 (ELF3-AS1) in the maintenance of genome integrity. We show that SCAT7 is upregulated in response to DNA-damaging drugs like cisplatin and camptothecin, where SCAT7 expression is required to promote cell survival. SCAT7 silencing leads to decreased proliferation of cisplatin-resistant cells in vitro and in vivo through interfering with cell cycle checkpoints and DNA repair molecular pathways. SCAT7 regulates ATR signaling, promoting homologous recombination. Importantly, SCAT7 also takes part in proteasome-mediated topoisomerase I (TOP1) degradation, and its depletion causes an accumulation of TOP1–cc structures responsible for the high levels of intrinsic DNA damage. Thus, our data demonstrate that SCAT7 is an important constituent of the DNA damage response pathway and serves as a potential therapeutic target for hard-to-treat drug resistant cancers.

Can graphene quantum dots cause DNA damage in cells?

Nanoscale ◽  
2015 ◽  
Vol 7 (21) ◽  
pp. 9894-9901 ◽  
Author(s):  
Dan Wang ◽  
Lin Zhu ◽  
Jian-Feng Chen ◽  
Liming Dai
Keyword(s):  
Dna Damage ◽  
Quantum Dots ◽  
Graphene Quantum Dots ◽  
In Cells
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