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

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.

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

DNA Repair ◽

10.1016/j.dnarep.2019.04.001 ◽

2019 ◽

Vol 78 ◽

pp. 114-127 ◽

Cited By ~ 9

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

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Yeast Rpn4 Links the Proteasome and DNA Repair via RAD52 Regulation

International Journal of Molecular Sciences ◽

10.3390/ijms21218097 ◽

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.

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ATM controls DNA repair and mitochondria transfer between neighboring cells

Cell Communication and Signaling ◽

10.1186/s12964-019-0472-x ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 2

Author(s):

Sha Jin ◽

Nils Cordes

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Dependent Manner ◽

Intercellular Signaling ◽

Tissue Integrity ◽

Damage Repair ◽

Repair Protein ◽

Mitochondria Transfer ◽

Dna Repair Protein ◽

Direct Cell

Abstract Intercellular communication is essential for multicellular tissue vitality and homeostasis. We show that healthy cells message protective signals through direct cell–cell connections to adjacent DNA–damaged cells in a microtubule–dependent manner. In DNA–damaged cells, mitochondria restoration is facilitated by fusion with undamaged mitochondria from healthy cells and their DNA damage repair is optimized in presence of healthy cells. Both, mitochondria transfer and intercellular signaling for an enhanced DNA damage response are critically regulated by the activity of the DNA repair protein ataxia telangiectasia mutated (ATM). These healthy–to–damaged prosurvival processes sustain normal tissue integrity and may be exploitable for overcoming resistance to therapy in diseases such as cancer.

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A CRISPR-associated factor Csa3a regulates DNA damage repair in Crenarchaeon Sulfolobus islandicus

Nucleic Acids Research ◽

10.1093/nar/gkaa694 ◽

2020 ◽

Vol 48 (17) ◽

pp. 9681-9693

Author(s):

Zhenzhen Liu ◽

Mengmeng Sun ◽

Jilin Liu ◽

Tao Liu ◽

Qing Ye ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Genomic Dna ◽

Cell Aggregation ◽

Gene Promoters ◽

Dna Damages ◽

Associated Factor ◽

Sulfolobus Islandicus ◽

Repair Systems

Abstract CRISPR−Cas system provides acquired immunity against invasive genetic elements in prokaryotes. In both bacteria and archaea, transcriptional factors play important roles in regulation of CRISPR adaptation and interference. In the model Crenarchaeon Sulfolobus islandicus, a CRISPR-associated factor Csa3a triggers CRISPR adaptation and activates CRISPR RNA transcription for the immunity. However, regulation of DNA repair systems for repairing the genomic DNA damages caused by the CRISPR self-immunity is less understood. Here, according to the transcriptome and reporter gene data, we found that deletion of the csa3a gene down-regulated the DNA damage response (DDR) genes, including the ups and ced genes. Furthermore, in vitro analyses demonstrated that Csa3a specifically bound the DDR gene promoters. Microscopic analysis showed that deletion of csa3a significantly inhibited DNA damage-induced cell aggregation. Moreover, the flow cytometry study and survival rate analysis revealed that the csa3a deletion strain was more sensitive to the DNA-damaging reagent. Importantly, CRISPR self-targeting and DNA transfer experiments revealed that Csa3a was involved in regulating Ups- and Ced-mediated repair of CRISPR-damaged host genomic DNA. These results explain the interplay between Csa3a functions in activating CRISPR adaptation and DNA repair systems, and expands our understanding of the lost link between CRISPR self-immunity and genome stability.

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Genomic instability in cancer: molecular mechanisms and therapeutic potentials

Current Pharmaceutical Design ◽

10.2174/1381612827666210426100206 ◽

2021 ◽

Vol 27 ◽

Author(s):

Arash Salmaninejad ◽

Khandan Ilkhani ◽

Havva Marzan ◽

Jamshid Gholizadeh Navashenaq ◽

Samira Rahimirad ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Genomic Instability ◽

Chromosomal Instability ◽

Molecular Mechanisms ◽

Cell Types ◽

Dna Damages ◽

Replication Errors ◽

Repair Mechanisms ◽

Dna Replication Errors

: DNA damage usually happens in all cell types, which may originate from endogenous sources, (i.e., DNA replication errors) or be emanated from radiations or chemicals. These damages range from changes in few nucleotides to large structural abnormalities on chromosomes and, if not repaired, could disturb the cellular homeostasis or cause cell death. DNA repair, as the most significant response to DNA damage, provides biological pathways by which DNA damages are corrected and returned into their natural circumstance. However, aberration in the DNA repair mechanisms may result in genomic and chromosomal instability and the accumulation of mutations. The activation of oncogenes and/or inactivation of tumor suppressor genes are serious consequence of genomic and chromosomal instability and may bring the cells into a cancerous phenotype. Therefore, genomic and chromosomal instability is usually considered as a crucial factor in the carcinogenesis and an important hallmark of various human malignancies. In the present study, we review our current understanding of the most updated mechanisms underlying genomic instability in cancer and discuss about the potential promises of these mechanisms in finding new targets for the treatment of cancer.

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

Blood ◽

10.1182/blood-2014-12-617282 ◽

2015 ◽

Vol 125 (26) ◽

pp. 4052-4059 ◽

Cited By ~ 18

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.

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IMPAIRMENT OF THE DNA REPAIR AND GROWTH ARREST PATHWAYS BY p53R2 SILENCING ENHANCES DNA DAMAGE- INDUCED APOPTOSIS IN A p53-DEPENDENT MANNER IN PROSTATE CANCER CELLS

The Journal of Urology ◽

10.1016/s0022-5347(08)61243-4 ◽

2008 ◽

Vol 179 (4S) ◽

pp. 424-424

Author(s):

Hong-lin Devlin ◽

Philip C Mack ◽

Rebekah A Burich ◽

Paul H Gumerlock ◽

Hsing-Jien Kung ◽

...

Keyword(s):

Prostate Cancer ◽

Dna Damage ◽

Dna Repair ◽

Cancer Cells ◽

Growth Arrest ◽

Dependent Manner ◽

Prostate Cancer Cells ◽

Induced Apoptosis

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Withaferin A Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress

Antioxidants ◽

10.3390/antiox10071063 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1063

Author(s):

Tsu-Ming Chien ◽

Kuang-Han Wu ◽

Ya-Ting Chuang ◽

Yun-Chiao Yeh ◽

Hui-Ru Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Bladder Cancer ◽

Cancer Cells ◽

Withaferin A ◽

Heme Oxygenase 1 ◽

Dependent Manner ◽

Dna Damages ◽

Bladder Cancer Cells ◽

Stress Dependent

Withaferin A (WFA), the Indian ginseng bioactive compound, exhibits an antiproliferation effect on several kinds of cancer, but it was rarely reported in bladder cancer cells. This study aims to assess the anticancer effect and mechanism of WFA in bladder cancer cells. WFA shows antiproliferation to bladder cancer J82 cells based on the finding of the MTS assay. WFA disturbs cell cycle progression associated with subG1 accumulation in J82 cells. Furthermore, WFA triggers apoptosis as determined by flow cytometry assays using annexin V/7-aminoactinomycin D and pancaspase detection. Western blotting also supports WFA-induced apoptosis by increasing cleavage of caspases 3, 8, and 9 and poly ADP-ribose polymerase. Mechanistically, WFA triggers oxidative stress-association changes, such as the generation of reactive oxygen species and mitochondrial superoxide and diminishment of the mitochondrial membrane potential, in J82 cells. In response to oxidative stresses, mRNA for antioxidant signaling, such as nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), superoxide dismutase 1 (SOD1), thioredoxin (TXN), glutathione-disulfide reductase (GSR), quinone dehydrogenase 1 (NQO1), and heme oxygenase 1 (HMOX1), are overexpressed in J82 cells. In addition, WFA causes DNA strand breaks and oxidative DNA damages. Moreover, the ROS scavenger N-acetylcysteine reverts all tested WFA-modulating effects. In conclusion, WFA possesses anti-bladder cancer effects by inducing antiproliferation, apoptosis, and DNA damage in an oxidative stress-dependent manner.

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The Tardigrade Damage Suppressor Protein Promotes Transcription Factor Activation and Expression of DNA Repair Genes in Human Cells in Response to Hydroxyl Radicals and UV-C Exposure

10.20944/preprints202107.0333.v1 ◽

2021 ◽

Author(s):

Claudia Ricci ◽

Giulia Riolo ◽

Carlotta Marzocchi ◽

Jlenia Brunetti ◽

Alessandro Pini ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Expression Patterns ◽

Dna Damage Repair ◽

Human Cells ◽

H2o2 Treatment ◽

Damage Repair ◽

Transcription Factor Activation ◽

Uv C ◽

Repair Genes

The Ramazzottius varieornatus tardigrade is an extremotolerant terrestrial invertebrate belonging to the phylum of Tardigrada. At a length of 0.1-1.0 mm, tardigrades are small animals with an exceptional tolerance to extreme conditions such as high pressure, chemicals and irradia-tion. These properties have been attributed to the recently-discovered Dsup protein. Dsup is a nucleosome-binding protein that prevents DNA damage against X-ray and oxidative stress without impairing cell life, also in Dsup-transfected animal and plant cells. However, the precise “protective” role of this protein is still under study. We performed experiments on human cells and shows that, as compared to control cells, Dsup+ cells are more resistant to UV-C exposure and H2O2. Real-time PCR identified different expression patterns of endogenous genes involved in apoptosis, cell survival and DNA damage repair in Dsup+ cells in response to H2O2 and UV-C. While H2O2 treatment in Dsup+ cells only marginally involved the activation of pathways responsible for DNA repair reinforcing the idea of a direct protective effect of the protein on DNA, in UV-C exposed cells, Dsup efficiently upregulates DNA damage repair genes. In conclusion, our data may help to delineate the different mechanisms by which the Dsup protein operates in response to different insults.

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A novel motif of Rad51 serves as an interaction hub for recombination auxiliary factors

eLife ◽

10.7554/elife.64131 ◽

2021 ◽

Vol 10 ◽

Author(s):

Negar Afshar ◽

Bilge Argunhan ◽

Maierdan Palihati ◽

Goki Taniguchi ◽

Hideo Tsubouchi ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Structural Analysis ◽

Homologous Recombination ◽

Genome Stability ◽

Single Motif ◽

Evolutionarily Conserved ◽

Recombinational Dna Repair

Homologous recombination (HR) is essential for maintaining genome stability. Although Rad51 is the key protein that drives HR, multiple auxiliary factors interact with Rad51 to potentiate its activity. Here, we present an interdisciplinary characterization of the interactions between Rad51 and these factors. Through structural analysis, we identified an evolutionarily conserved acidic patch of Rad51. The neutralization of this patch completely abolished recombinational DNA repair due to defects in the recruitment of Rad51 to DNA damage sites. This acidic patch was found to be important for the interaction with Rad55-Rad57 and essential for the interaction with Rad52. Furthermore, biochemical reconstitutions demonstrated that neutralization of this acidic patch also impaired the interaction with Rad54, indicating that a single motif is important for the interaction with multiple auxiliary factors. We propose that this patch is a fundamental motif that facilitates interactions with auxiliary factors and is therefore essential for recombinational DNA repair.

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