scholarly journals A Direct Interaction Between P53-Binding Protein 1 and Minichromosome Maintenance Complex in Hepg2 Cells

2018 ◽  
Vol 47 (6) ◽  
pp. 2350-2359 ◽  
Author(s):  
Yong Chen ◽  
Chengyin Weng ◽  
Hui Zhang ◽  
Jianqun Sun ◽  
Yawei Yuan
Keyword(s):  
Dna Damage ◽  
Hepg2 Cell ◽  
Hepg2 Cells ◽  
Binding Protein ◽  
Direct Interaction ◽  
Potential Interaction ◽  
Cell Nuclei ◽  
Minichromosome Maintenance ◽  
Chromatin Fraction ◽  
Hepatoma Hepg2

Background/Aims: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. DNA damage repair in cancer cells is a promising approach for the treatment of cancers. We aimed to explore the potential interaction between p53-binding protein 1 (53BP1) and minichromosome maintenance (MCMs) proteins during DNA damage in human hepatoma HepG2 cells. Methods: The recombinant vectors of 53BP1 and MCMs with tags were constructed and transfected into HepG2 cells. Immunoprecipitation (IP) and mass spectrometry (MS) were performed to identify the possible interactions between 53BP1 and MCMs, and glutathione S-transferase (GST) pull-down assay was carried out to detect the direct interaction. Moreover, the expressions of MCM2 and MCM6 were suppressed by specific short hairpin RNAs (shRNAs), and then the chromatin fraction and foci formation of 53BP1 were examined under the condition of DNA damage. Results: The results showed that MCM2/3/5/6 was immunoprecipitated against the hemaglutinin (HA)-tagged 53BP1 in HepG2 cell nuclei. GST results revealed that there was a direct interaction between 53BP1 and MCMs complex. Moreover, the non-chromatin level of 53BP1 was significantly increased by down-regulation of MCM2 or MCM6, but was statistically decreased the chromatin level. Furthermore, we observed that knockdown of MCM2 or MCM6 could statistically inhibit the foci formation of 53BP1 in HepG2 cell nuclei upon bleomycin-induced DNA damage (P < 0.01). Conclusion: Our results suggest that there is a direct interaction between 53BP1 and MCMs, which is essential for 53BP1 chromatin fraction and foci formation in hepatoma HepG2 cells.

Novel Health Supplement for Recovery of Alcohol Induced Adverse Effects and Associated Disorders: HepG2 Cells Study and Safety Dose Profiling on Rats

2021 ◽  
Vol 7 (5) ◽  
pp. 1-9
Author(s):  
Neelesh Kumar Nema ◽  
Keyword(s):  
Adverse Effects ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Plant Extracts ◽  
Hepg2 Cells ◽  
Human Hepatoma ◽  
Hepg2 Cell Line ◽  
Study Objective ◽  
Hepatoma Hepg2

The present study objective was to design and develop novel health-supplement formula from plant extracts and was to evaluate the formula for high episodic alcohol toxicities, and associated disorders against alcohol intoxicated and oxidative damaged Human Hepatoma HepG2 cell line.

scholarly journals DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2nanoparticles in human hepatoma HepG2 cells

2010 ◽  
Vol 5 (3) ◽  
pp. 341-353 ◽  
Author(s):  
Jana PetkoviĆ ◽  
Bojana Žegura ◽  
Magdalena StevanoviĆ ◽  
Nataša Drnovšek ◽  
Dragan UskokoviĆ ◽  
...  
Keyword(s):  
Dna Damage ◽  
Hepg2 Cells ◽  
Human Hepatoma ◽  
Human Hepatoma Hepg2 Cells ◽  
Hepatoma Hepg2

scholarly journals HO-1 and Heme: G-Quadruplex Interaction Choreograph DNA Damage Responses and Cancer Growth

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1801
Author(s):  
Giacomo Canesin ◽  
Anindhita Meena Muralidharan ◽  
Kenneth D. Swanson ◽  
Barbara Wegiel
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Direct Interaction ◽  
Cancer Therapeutics ◽  
Suppressor Gene ◽  
Cancer Growth ◽  
Heme Oxygenase 1 ◽  
Cell Nuclei ◽  
Dna Damage Responses

Many anti-cancer therapeutics lead to the release of danger associated pattern molecules (DAMPs) as the result of killing large numbers of both normal and transformed cells as well as lysis of red blood cells (RBC) (hemolysis). Labile heme originating from hemolysis acts as a DAMP while its breakdown products exert varying immunomodulatory effects. Labile heme is scavenged by hemopexin (Hx) and processed by heme oxygenase-1 (HO-1, Hmox1), resulting in its removal and the generation of biliverdin/bilirubin, carbon monoxide (CO) and iron. We recently demonstrated that labile heme accumulates in cancer cell nuclei in the tumor parenchyma of Hx knockout mice and contributes to the malignant phenotype of prostate cancer (PCa) cells and increased metastases. Additionally, this work identified Hx as a tumor suppressor gene. Direct interaction of heme with DNA G-quadruplexes (G4) leads to altered gene expression in cancer cells that regulate transcription, recombination and replication. Here, we provide new data supporting the nuclear role of HO-1 and heme in modulating DNA damage response, G4 stability and cancer growth. Finally, we discuss an alternative role of labile heme as a nuclear danger signal (NDS) that regulates gene expression and nuclear HO-1 regulated DNA damage responses stimulated by its interaction with G4.

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