Cell Cycle Resolved Measurements of Poly(ADP-Ribose) Formation and DNA Damage Signaling by Quantitative Image-Based Cytometry

2017 ◽  
pp. 57-68 ◽  
Author(s):  
Jone Michelena ◽  
Matthias Altmeyer
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Damage Signaling ◽  
Quantitative Image

Cell cycle control and DNA-damage signaling in mammals

2021 ◽  
pp. 237-255
Author(s):  
R. Gundogdu ◽  
A. Hergovich ◽  
V. Gómez
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Control ◽  
Dna Damage Signaling

scholarly journals Differentiation-Induced Radioresistance in Muscle Cells

2004 ◽  
Vol 24 (14) ◽  
pp. 6350-6361 ◽  
Author(s):  
Lucia Latella ◽  
Jiri Lukas ◽  
Cristiano Simone ◽  
Pier Lorenzo Puri ◽  
Jiri Bartek
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Double Strand Breaks ◽  
Proliferating Cells ◽  
Histone H2ax ◽  
Selective Blockade ◽  
Differentiated Cells ◽  
Dna Damage Signaling ◽  
Ataxia Teleangiectasia ◽  
Associated Proteins

ABSTRACT DNA damage induces cell cycle arrest and DNA repair or apoptosis in proliferating cells. Terminally differentiated cells are permanently withdrawn from the cell cycle and partly resistant to apoptosis. To investigate the effects of genotoxic agents in postmitotic cells, we compared DNA damage-activated responses in mouse and human proliferating myoblasts and their differentiated counterparts, the myotubes. DNA double-strand breaks caused by ionizing radiation (IR) induced rapid activating autophosphorylation of ataxia-teleangiectasia-mutated (ATM), phosphorylation of histone H2AX, recruitment of repair-associated proteins MRE11 and Nbs1, and activation of Chk2 in both myoblasts and myotubes. However, IR-activated, ATM-mediated phosphorylation of p53 at serine 15 (human) or 18 (mouse) [Ser15(h)/18(m)], and apoptosis occurred in myoblasts but was impaired in myotubes. This phosphorylation could be enforced in myotubes by the anthracycline derivative doxorubicin, leading to selective activation of proapoptotic genes. Unexpectedly, the abundance of autophosphorylated ATM was indistinguishable after exposure of myotubes to IR (10 Gy) or doxorubicin (1 μM/24 h) despite efficient phosphorylation of p53 Ser15(h)/18(m), and apoptosis occurred only in response to doxorubicin. These results suggest that radioresistance in myotubes might reflect a differentiation-associated, pathway-selective blockade of DNA damage signaling downstream of ATM. This mechanism appears to preserve IR-induced activation of the ATM-H2AX-MRE11/Rad50/Nbs1 lesion processing and repair pathway yet restrain ATM-p53-mediated apoptosis, thereby contributing to life-long maintenance of differentiated muscle tissues.

scholarly journals DNA damage signaling, impairment of cell cycle progression, and apoptosis triggered by 5-ethynyl-2′-deoxyuridine incorporated into DNA

2013 ◽  
Vol 83 (11) ◽  
pp. 979-988 ◽  
Author(s):  
Hong Zhao ◽  
H. Dorota Halicka ◽  
Jiangwei Li ◽  
Ewa Biela ◽  
Krzysztof Berniak ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Dna Damage Signaling

scholarly journals Novel tetrahydroacridine and cyclopentaquinoline derivatives with fluorobenzoic acid moiety induce cell cycle arrest and apoptosis in lung cancer cells by activation of DNA damage signaling

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769501 ◽  
Author(s):  
Paweł Szymański ◽  
Paulina Olszewska ◽  
Elżbieta Mikiciuk-Olasik ◽  
Antoni Różalski ◽  
Agnieszka Maszewska ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Cyclin Dependent Kinase ◽  
Induce Cell Cycle Arrest ◽  
Dna Damage Signaling ◽  
Cycle Arrest

Lung cancer is still the leading cause of cancer-related death worldwide, indicating a necessity to develop more effective therapy. Acridine derivatives are potential anticancer agents due to their ability to intercalate DNA as well as inhibit enzymes involved in replication and transcription. Recently, we have evaluated anticancer activity of 32 novel acridine-based compounds. We found that the most effective were tetrahydroacridine and cyclopentaquinoline derivatives with fluorobenzoic acid containing eight and nine carbon atoms in the aliphatic chain. The aim of this study was to determine the molecular mechanisms of compounds-induced cell cycle arrest and apoptosis in human lung adenocarcinoma cells. All compounds activated Ataxia telangiectasia mutated kinase and phosphorylated histone H2A.X at Ser139 indicating DNA damage. Treatment of cells with the compounds increased phosphorylation and accumulation of p53 that regulate cell cycle as well as apoptosis. All compounds induced G0/1 cell cycle arrest by phosphorylation of cyclin-dependent kinase 2 at Tyr15 resulting in attenuation of the kinase activity. In addition, cyclopentaquinoline derivatives induced expression of cyclin-dependent kinase 2 inhibitor, p21; however, tetrahydroacridine derivatives had no significant effect on p21. Moreover, all compounds decreased the mitochondrial membrane potential accompanied by increased expression of Bax and down-regulation of Bcl-2, suggesting activation of the mitochondrial pathway. All compounds also significantly attenuated the migration rates of lung cancer cells. Collectively, our findings suggest a central role of activation of DNA damage signaling in response to new acridine derivatives treatment to induce cell cycle arrest and apoptosis in cancer cells and provide support for their further development as potential drug candidates.

Usnic Acid Inhibits Proliferation and Migration through ATM Mediated DNA Damage Response in RKO Colorectal Cancer Cell

2020 ◽  
Vol 21 ◽  
Author(s):  
Wenbing Wu ◽  
Hui Gou ◽  
Jingying Dong ◽  
Xiaolong Yang ◽  
Yanan Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Dna Damage ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Usnic Acid ◽  
Chemotherapeutic Drugs ◽  
Dna Damage Signaling ◽  
And Migration ◽  
Proliferation And Migration

Background: Usnic acid (UA), also known as lichenol, has been reported to have inhibitory effects on a variety of cancer cells, but its specific mechanism remained to be elucidated. Tumor chemotherapy drugs, especially DNA damage chemotherapeutic drugs target Chromosomal DNA, but their spontaneous and acquired drug resistance are also an urgent problem to be solved. Therefore, drug combination research has become the focus of researchers. Methods: Here, we evaluated the tumor-suppressing molecular mechanism of UA in colorectal cancer cells RKO from the perspective of ATM-mediated DNA damage signaling pathway through H2O2 simulating DNA damage chemotherapeutic drugs. CCK8 cell proliferation assay was used to determine the inhibition of RKO cells by hydrogen peroxide and UA alone or in combination, and wound healing assay was applied to determine the effect of the drug on cell migration. Results: Transfected cells with miRNA18a-5p mimics and inhibitors, MDC and DCFH-DA staining for the measurement of autophagy and ROS, cell cycle and apoptosis were detected by flow cytometry, expressions of microRNA and mRNA were determined by fluorescence quantitative PCR, and protein by Western blot. Discussion: We found that UA can up-regulate ATM via miR-18a to activate DNA damage signaling pathway and inhibit the proliferation and migration of RKO cells in a concentration-dependent manner. Conclusion: At the same time, DNA damage responses including cell cycle, autophagy, apoptosis and ROS levels are also regulated by UA respectively. Therefore, UA combined with DNA damage chemotherapeutic drugs may be an effective treatment for cancer.

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