scholarly journals Ebf1 heterozygosity results in increased DNA damage in pro-B cells and their synergistic transformation by Pax5 haploinsufficiency

Blood ◽  
2015 ◽  
Vol 125 (26) ◽  
pp. 4052-4059 ◽  
Author(s):  
Mahadesh A. J. Prasad ◽  
Jonas Ungerbäck ◽  
Josefine Åhsberg ◽  
Rajesh Somasundaram ◽  
Tobias Strid ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
B Cells ◽  
Dependent Manner ◽  
Key Points ◽  
Leukemia Development ◽  
Dose Dependent

Key Points Ebf1 regulates DNA repair in a dose-dependent manner. Combined heterozygote loss of Ebf1 and Pax5 predisposes for leukemia development.

scholarly journals Tyrosine phosphorylation of guanosine triphosphatase activating protein by activation via surface IgG in human B cells

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1535-1539
Author(s):  
H Yagura ◽  
N Oyaizu ◽  
S Pahwa
Keyword(s):  
B Cells ◽  
Tyrosine Phosphorylation ◽  
Signal Transduction Pathway ◽  
Dependent Manner ◽  
Transduction Pathway ◽  
Gtpase Activating Protein ◽  
Human B Cells ◽  
Associated Proteins ◽  
Guanosine Triphosphatase ◽  
Dose Dependent

In this study, we analyzed tyrosine phosphorylation of guanosine triphosphatase (GTPase) activating protein in human B cells stimulated through surface IgG, using Western blot and immunoprecipitation. Stimulation through surface IgG induced the tyrosine phosphorylation of GTPase-activating protein (GAP) and two associated proteins, a 190-Kd protein and a 62-Kd protein, within 1 minute and in a dose-dependent manner. This tyrosine phosphorylation was blocked by Genistein (Extrasynthese, Genay, France). These data suggest that GTPase- activating protein is involved in a signal transduction pathway initiated from surface IgG in human B cells.

PML nuclear bodies are recruited to persistent DNA damage lesions in an RNF168-53BP1 dependent manner and contribute to DNA repair

DNA Repair ◽  
2019 ◽  
Vol 78 ◽  
pp. 114-127 ◽  
Author(s):  
Marketa Vancurova ◽  
Hana Hanzlikova ◽  
Lucie Knoblochova ◽  
Jan Kosla ◽  
Dusana Majera ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Nuclear Bodies ◽  
Dependent Manner ◽  
Pml Nuclear Bodies

scholarly journals Cytotoxic Effects of Air Freshener Biocides in Lung Epithelial Cells

2013 ◽  
Vol 8 (9) ◽  
pp. 1934578X1300800
Author(s):  
Jung-Taek Kwon ◽  
Mimi Lee ◽  
Gun-Baek Seo ◽  
Hyun-Mi Kim ◽  
Ilseob Shim ◽  
...  
Keyword(s):  
Dna Damage ◽  
Epithelial Cells ◽  
Cell Viability ◽  
Lung Epithelial Cells ◽  
Ros Generation ◽  
Dependent Manner ◽  
Cytotoxic Effects ◽  
Lung Epithelial ◽  
Dose Dependent ◽  
A549 Lung

This study evaluated the cytotoxicity of mixtures of citral (CTR) and either benzisothiazolinone (BIT, Mix-CTR-BIT) or triclosan (TCS, Mix-CTR-TCS) in human A549 lung epithelial cells. We investigated the effects of various mix ratios of these common air freshener ingredients on cell viability, cell proliferation, reactive oxygen species (ROS) generation, and DNA damage. Mix-CTR-BIT and Mix-CTR-TCS significantly decreased the viability of lung epithelial cells and inhibited cell growth in a dose-dependent manner. In addition, both mixtures increased ROS generation, compared to that observed in control cells. In particular, cell viability, growth, and morphology were affected upon increase in the proportion of BIT or TCS in the mixture. However, comet analysis showed that treatment of cells with Mix-CTR-BIT or Mix-CTR-TCS did not increase DNA damage. Taken together, these data suggested that increasing the content of biocides in air fresheners might induce cytotoxicity, and that screening these compounds using lung epithelial cells may contribute to hazard assessment.

Kaempferol Induces DNA Damage and Inhibits DNA Repair Associated Protein Expressions in Human Promyelocytic Leukemia HL-60 Cells

2015 ◽  
Vol 43 (02) ◽  
pp. 365-382 ◽  
Author(s):  
Lung-Yuan Wu ◽  
Hsu-Feng Lu ◽  
Yu-Cheng Chou ◽  
Yung-Luen Shih ◽  
Da-Tian Bau ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Protein Expression ◽  
Ataxia Telangiectasia ◽  
Repair System ◽  
Dapi Staining ◽  
Viable Cells ◽  
Protein Expressions ◽  
Dose Dependent

Numerous evidences have shown that plant flavonoids (naturally occurring substances) have been reported to have chemopreventive activities and protect against experimental carcinogenesis. Kaempferol, one of the flavonoids, is widely distributed in fruits and vegetables, and may have cancer chemopreventive properties. However, the precise underlying mechanism regarding induced DNA damage and suppressed DNA repair system are poorly understood. In this study, we investigated whether kaempferol induced DNA damage and affected DNA repair associated protein expression in human leukemia HL-60 cells in vitro. Percentages of viable cells were measured via a flow cytometry assay. DNA damage was examined by Comet assay and DAPI staining. DNA fragmentation (ladder) was examined by DNA gel electrophoresis. The changes of protein levels associated with DNA repair were examined by Western blotting. Results showed that kaempferol dose-dependently decreased the viable cells. Comet assay indicated that kaempferol induced DNA damage (Comet tail) in a dose-dependent manner and DAPI staining also showed increased doses of kaempferol which led to increased DNA condensation, these effects are all of dose-dependent manners. Western blotting indicated that kaempferol-decreased protein expression associated with DNA repair system, such as phosphate-ataxia-telangiectasia mutated (p-ATM), phosphate-ataxia-telangiectasia and Rad3-related (p-ATR), 14-3-3 proteins sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK), O6-methylguanine-DNA methyltransferase (MGMT), p53 and MDC1 protein expressions, but increased the protein expression of p-p53 and p-H2AX. Protein translocation was examined by confocal laser microscopy, and we found that kaempferol increased the levels of p-H2AX and p-p53 in HL-60 cells. Taken together, in the present study, we found that kaempferol induced DNA damage and suppressed DNA repair and inhibited DNA repair associated protein expression in HL-60 cells, which may be the factors for kaempferol induced cell death in vitro.

scholarly journals Exploring the effect of UV-C radiation on earthworm and understanding its genomic integrity in the context of H2AX expression

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Karthikeyan Subbiahanadar Chelladurai ◽  
Jackson Durairaj Selvan Christyraj ◽  
Ananthaselvam Azhagesan ◽  
Vennila Devi Paulraj ◽  
Muralidharan Jothimani ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Primary Response ◽  
Coelomic Fluid ◽  
Dependent Manner ◽  
Perionyx Excavatus ◽  
Dna Damages ◽  
Highly Sensitive ◽  
Evolutionarily Conserved ◽  
Uv C

AbstractMaintaining genomic stability is inevitable for organism survival and it is challenged by mutagenic agents, which include ultraviolet (UV) radiation. Whenever DNA damage occurs, it is sensed by DNA-repairing proteins and thereby performing the DNA-repair mechanism. Specifically, in response to DNA damage, H2AX is a key protein involved in initiating the DNA-repair processes. In this present study, we investigate the effect of UV-C on earthworm, Perionyx excavatus and analyzed the DNA-damage response. Briefly, we expose the worms to different doses of UV-C and find that worms are highly sensitive to UV-C. As a primary response, earthworms produce coelomic fluid followed by autotomy. However, tissue inflammation followed by death is observed when we expose worm to increased doses of UV-C. In particular, UV-C promotes damages in skin layers and on the contrary, it mediates the chloragogen and epithelial outgrowth in intestinal tissues. Furthermore, UV-C promotes DNA damages followed by upregulation of H2AX on dose-dependent manner. Our finding confirms DNA damage caused by UV-C is directly proportional to the expression of H2AX. In short, we conclude that H2AX is present in the invertebrate earthworm, which plays an evolutionarily conserved role in DNA damage event as like that in higher animals.

scholarly journals Yeast Rpn4 Links the Proteasome and DNA Repair via RAD52 Regulation

2020 ◽  
Vol 21 (21) ◽  
pp. 8097
Author(s):  
Daria S. Spasskaya ◽  
Nonna I. Nadolinskaia ◽  
Vera V. Tutyaeva ◽  
Yuriy P. Lysov ◽  
Vadim L. Karpov ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Proteasome Inhibition ◽  
26S Proteasome ◽  
Dependent Manner ◽  
Dna Repair Genes ◽  
Damage Resistance ◽  
Dna Damaging Agents ◽  
Mutant Strains ◽  
Repair Genes

Environmental and intracellular factors often damage DNA, but multiple DNA repair pathways maintain genome integrity. In yeast, the 26S proteasome and its transcriptional regulator and substrate Rpn4 are involved in DNA damage resistance. Paradoxically, while proteasome dysfunction may induce hyper-resistance to DNA-damaging agents, Rpn4 malfunction sensitizes yeasts to these agents. Previously, we proposed that proteasome inhibition causes Rpn4 stabilization followed by the upregulation of Rpn4-dependent DNA repair genes and pathways. Here, we aimed to elucidate the key Rpn4 targets responsible for DNA damage hyper-resistance in proteasome mutants. We impaired the Rpn4-mediated regulation of candidate genes using the CRISPR/Cas9 system and tested the sensitivity of mutant strains to 4-NQO, MMS and zeocin. We found that the separate or simultaneous deregulation of 19S or 20S proteasome subcomplexes induced MAG1, DDI1, RAD23 and RAD52 in an Rpn4-dependent manner. Deregulation of RAD23, DDI1 and RAD52 sensitized yeast to DNA damage. Genetic, epigenetic or dihydrocoumarin-mediated RAD52 repression restored the sensitivity of the proteasome mutants to DNA damage. Our results suggest that the Rpn4-mediated overexpression of DNA repair genes, especially RAD52, defines the DNA damage hyper-resistant phenotype of proteasome mutants. The developed yeast model is useful for characterizing drugs that reverse the DNA damage hyper-resistance phenotypes of cancers.

scholarly journals Pedigree analyses of yeast cells recovering from DNA damage allow assignment of lethal events to individual post-treatment generations.

Genetics ◽  
1990 ◽  
Vol 124 (1) ◽  
pp. 57-65
Author(s):  
F Klein ◽  
A Karwan ◽  
U Wintersberger
Keyword(s):  
Dna Damage ◽  
Post Treatment ◽  
Yeast Cells ◽  
Dependent Manner ◽  
The Third ◽  
Lethal Mutations ◽  
Dna Damaging Agents ◽  
Kinetics Of ◽  
Dose Dependent ◽  
Insight Into

Abstract Haploid cells of Saccharomyces cerevisiae were treated with different DNA damaging agents at various doses. A study of the progeny of individual such cells (by pedigree analyses up to the third generation) allowed the assignment of lethal events to distinct post treatment generations. By microscopically inspecting those cells which were not able to form visible colonies we could discriminate between cells dying from immediately effective lethal hits and those generating microcolonies (three to several hundred cells) probably as a consequence of lethal mutation(s). The experimentally obtained numbers of lethal events (which we call apparent lethal fixations) were mathematically transformed into mean probabilities of lethal fixations as taking place in cells of certain post treatment generations. Such analyses give detailed insight into the kinetics of lethality as a consequence of different kinds of DNA damage. For example, X-irradiated cells lost viability mainly by lethal hits (which we call 00-fixations); only at a higher dose also lethal mutations fixed in the cells that were in direct contact with the mutagen (which we call 0-fixations), but not in later generations, occurred. Ethyl methanesulfonate (EMS)-treated cells were hit by 00-fixations in a dose dependent manner; 0-fixations were not detected for any dose of EMS applied; the probability for fixation of lethal mutations was found equally high for cells of the first and second post treatment generation and, unexpectedly, was well above control in the third post-treatment generation. The distribution of all sorts of lethal fixations taken together, which occurred in the EMS-damaged cell families, was not random.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Artemisinin derivative SM934, influences the activation, proliferation, differentiation and antibody-secreting capacity of β-cells in systemic lupus erythematosus mice via inhibition of TLR7/9 signaling pathway

2021 ◽  
Vol 18 (7) ◽  
pp. 1391-1396
Author(s):  
Yajuan Li ◽  
Lixin Zhao ◽  
Xuehui Yang ◽  
Jing Chen ◽  
Wenjing Xu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
B Lymphocyte ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Artemisinin Derivative ◽  
Systemic Lupus ◽  
Dose Dependent

Purpose: To study the influence of artemisinin derivative, SM934 on activation, proliferation, differentiation and antibody-secreting capacity of B cells of systemic lupus erythematosus (SLE) mice, and the underlying mechanism. Methods: Female MRL/lpr mice (n = 60) were randomly assigned to four groups of 15 mice each: SLE, 2.5 mg/kg SM934; 5 mg/kg SM934, and 10 mg/kg SM934 groups. Serum levels of interleukins 6, 10, 17 and 21 (IL-6, IL-17, IL-10 and IL-21) were determined. The secretions of immunoglobulins G and M (IgG and IgM) by B cells were determined. The population of B lymphocyte subtypes was determined flow cytometrically. The expressions of Blimp-1 and Bcl-6, Toll-like receptors 7 and 9 (TLR7 and TLR9) mRNAs were determined. Results: SLE-induced upregulation of serum IL-10, IL-6, IL-17 and IL-21 was significantly and dosedependently reduced following a 2-month treatment with SM934 (p < 0.01). Treatment with SM934 significantly and dose-dependently accentuated B cell germinal center B cell populations, but significantly and dose-dependently decreased the populations of plasma and activated B cells (p < 0.01). The splenic levels of IgG and IgM were decreased in a dose-dependent fashion after 8 weeks of treatment (p < 0.01). Artemisinin derivative SM934 decreased the expression of Blimp-1, and upregulated the expression of Bcl-6, both in a dose-dependent manner (p < 0.01). Moreover, SM934 decreased the mRNA expressions of TLR7 and TLR9 in a dose-based manner (p < 0.01). Conclusion: Artemisinin derivative SM934 mitigates LSE syndromes by suppressing the TLR-induced B-cell stimulation and plasma cell generation

scholarly journals Tyrosine phosphorylation of guanosine triphosphatase activating protein by activation via surface IgG in human B cells

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1535-1539 ◽  
Author(s):  
H Yagura ◽  
N Oyaizu ◽  
S Pahwa
Keyword(s):  
B Cells ◽  
Tyrosine Phosphorylation ◽  
Signal Transduction Pathway ◽  
Dependent Manner ◽  
Transduction Pathway ◽  
Gtpase Activating Protein ◽  
Human B Cells ◽  
Associated Proteins ◽  
Guanosine Triphosphatase ◽  
Dose Dependent

Abstract In this study, we analyzed tyrosine phosphorylation of guanosine triphosphatase (GTPase) activating protein in human B cells stimulated through surface IgG, using Western blot and immunoprecipitation. Stimulation through surface IgG induced the tyrosine phosphorylation of GTPase-activating protein (GAP) and two associated proteins, a 190-Kd protein and a 62-Kd protein, within 1 minute and in a dose-dependent manner. This tyrosine phosphorylation was blocked by Genistein (Extrasynthese, Genay, France). These data suggest that GTPase- activating protein is involved in a signal transduction pathway initiated from surface IgG in human B cells.

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