scholarly journals Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies

2020 ◽  
Vol 21 (19) ◽  
pp. 7264
Author(s):  
Mateusz Kciuk ◽  
Beata Marciniak ◽  
Mariusz Mojzych ◽  
Renata Kontek
Keyword(s):  
Dna Damage ◽  
Uv Radiation ◽  
Cellular Response ◽  
Current Knowledge ◽  
Uv Light ◽  
Environmental Pollutants ◽  
Ozone Layer ◽  
Special Focus ◽  
Dna Damage And Repair ◽  
Protective Strategies

The protective ozone layer is continually depleting due to the release of deteriorating environmental pollutants. The diminished ozone layer contributes to excessive exposure of cells to ultraviolet (UV) radiation. This leads to various cellular responses utilized to restore the homeostasis of exposed cells. DNA is the primary chromophore of the cells that absorbs sunlight energy. Exposure of genomic DNA to UV light leads to the formation of multitude of types of damage (depending on wavelength and exposure time) that are removed by effectively working repair pathways. The aim of this review is to summarize current knowledge considering cellular response to UV radiation with special focus on DNA damage and repair and to give a comprehensive insight for new researchers in this field. We also highlight most important future prospects considering application of the progressing knowledge of UV response for the clinical control of diverse pathologies.

scholarly journals Cellular response to DNA damage is enhanced by the pR plasmid in mouse cells and in Escherichia coli.

1986 ◽  
Vol 6 (2) ◽  
pp. 586-592 ◽  
Author(s):  
L Marcucci ◽  
F Gigliani ◽  
P A Battaglia ◽  
R Bosi ◽  
E Sporeno ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Statistical Analysis ◽  
Cellular Response ◽  
Regulatory Mechanism ◽  
Uv Light ◽  
Transformed Cells ◽  
Insertion Mutagenesis ◽  
Mouse Cells ◽  
Inducible Repair

The pR plasmid, which enhances the survival of Escherichia coli C600 exposed to UV light by induction of the SOS regulatory mechanism, showed the same effect when it transformed mouse LTA cells (tk-, aprt-). With Tn5 insertion mutagenesis which inactivates UV functions in the pR plasmid, we recognized two different regions of the plasmid, uvp1 and uvp2. These pR UVR- mutants exhibited the same effect in LTA transformed cells, demonstrating that resistance to UV light, carried by the pR plasmid, was really due to the expression of these two regions, which were also in the mouse cells. Statistical analysis showed that the expression of the uvp1 and uvp2 regions significantly increased (P less than 0.01) the survival upon exposure to UV light in mouse cells and bacteria. These results might suggest the presence of an inducible repair response to DNA damage in mouse LTA cells.

scholarly journals DNA damage and repair proteins in cellular response to sulfur mustard in Iranian veterans more than two decades after exposure

2018 ◽  
Vol 293 ◽  
pp. 67-72 ◽  
Author(s):  
Shahriar Khateri ◽  
Mahdi Balali-Mood ◽  
Peter Blain ◽  
Faith Williams ◽  
Paul Jowsey ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cellular Response ◽  
Sulfur Mustard ◽  
Dna Damage And Repair

scholarly journals Topoisomerase III Acts Upstream of Rad53p in the S-Phase DNA Damage Checkpoint

2001 ◽  
Vol 21 (21) ◽  
pp. 7150-7162 ◽  
Author(s):  
Ronjon K. Chakraverty ◽  
Jonathan M. Kearsey ◽  
Thomas J. Oakley ◽  
Muriel Grenon ◽  
Maria-Angeles de la Torre Ruiz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cellular Response ◽  
Cell Cycle Progression ◽  
Uv Light ◽  
S Phase ◽  
Dna Damaging Agents ◽  
Topoisomerase Iii ◽  
Rad53 Kinase ◽  
S Phase Checkpoint

ABSTRACT Deletion of the Saccharomyces cerevisiae TOP3gene, encoding Top3p, leads to a slow-growth phenotype characterized by an accumulation of cells with a late S/G2content of DNA (S. Gangloff, J. P. McDonald, C. Bendixen, L. Arthur, and R. Rothstein, Mol. Cell. Biol. 14:8391–8398, 1994). We have investigated the function of TOP3 during cell cycle progression and the molecular basis for the cell cycle delay seen in top3Δ strains. We show that top3Δ mutants exhibit a RAD24-dependent delay in the G2 phase, suggesting a possible role for Top3p in the resolution of abnormal DNA structures or DNA damage arising during S phase. Consistent with this notion,top3Δ strains are sensitive to killing by a variety of DNA-damaging agents, including UV light and the alkylating agent methyl methanesulfonate, and are partially defective in the intra-S-phase checkpoint that slows the rate of S-phase progression following exposure to DNA-damaging agents. This S-phase checkpoint defect is associated with a defect in phosphorylation of Rad53p, indicating that, in the absence of Top3p, the efficiency of sensing the existence of DNA damage or signaling to the Rad53 kinase is impaired. Consistent with a role for Top3p specifically during S phase, top3Δ mutants are sensitive to the replication inhibitor hydroxyurea, expression of the TOP3 mRNA is activated in late G1 phase, and DNA damage checkpoints operating outside of S phase are unaffected by deletion of TOP3. All of these phenotypic consequences of loss of Top3p function are at least partially suppressed by deletion of SGS1, the yeast homologue of the human Bloom's and Werner's syndrome genes. These data implicate Top3p and, by inference, Sgs1p in an S-phase-specific role in the cellular response to DNA damage. A model proposing a role for these proteins in S phase is presented.

scholarly journals All You Need Is Light. Photorepair of UV-Induced Pyrimidine Dimers

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1304
Author(s):  
Agnieszka Katarzyna Banaś ◽  
Piotr Zgłobicki ◽  
Ewa Kowalska ◽  
Aneta Bażant ◽  
Dariusz Dziga ◽  
...  
Keyword(s):  
Dna Damage ◽  
Uv Light ◽  
High Energy ◽  
Solar Irradiation ◽  
Visible Range ◽  
Special Focus ◽  
Special Importance ◽  
Pyrimidine Dimers ◽  
Uva Light ◽  
Dna Strand

Although solar light is indispensable for the functioning of plants, this environmental factor may also cause damage to living cells. Apart from the visible range, including wavelengths used in photosynthesis, the ultraviolet (UV) light present in solar irradiation reaches the Earth’s surface. The high energy of UV causes damage to many cellular components, with DNA as one of the targets. Putting together the puzzle-like elements responsible for the repair of UV-induced DNA damage is of special importance in understanding how plants ensure the stability of their genomes between generations. In this review, we have presented the information on DNA damage produced under UV with a special focus on the pyrimidine dimers formed between the neighboring pyrimidines in a DNA strand. These dimers are highly mutagenic and cytotoxic, thus their repair is essential for the maintenance of suitable genetic information. In prokaryotic and eukaryotic cells, with the exception of placental mammals, this is achieved by means of highly efficient photorepair, dependent on blue/UVA light, which is performed by specialized enzymes known as photolyases. Photolyase properties, as well as their structure, specificity and action mechanism, have been briefly discussed in this paper. Additionally, the main gaps in our knowledge on the functioning of light repair in plant organelles, its regulation and its interaction between different DNA repair systems in plants have been highlighted.

scholarly journals Towards a Better Understanding of the Molecular Mechanisms Involved in Sunlight-Induced Melanoma

2005 ◽  
Vol 2005 (1) ◽  
pp. 57-61 ◽  
Author(s):  
Mandy Williams ◽  
Allal Ouhtit
Keyword(s):  
Skin Cancer ◽  
Uv Radiation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Uv Light ◽  
Laboratory Animals ◽  
Environmental Carcinogen ◽  
Biological Studies ◽  
Significant Gene ◽  
Recent Developments

Although much less prevalent than its nonmelanoma skin cancer counterparts, cutaneous malignant melanoma (CMM) is the most lethal human skin cancer. Epidemiological and biological studies have established a strong link between lifetime exposure to ultraviolet (UV) light, particularly sunburn in childhood, and the development of melanoma. However, the specific molecular targets of this environmental carcinogen are not known. Data obtained from genetic and molecular studies over the last few years have identified the INK4a/ARF locus as the “gatekeeper” melanoma suppressor, encoding two tumour suppressor proteins in human, p16INK4aand p14ARF. Recent developments in molecular biotechnology and research using laboratory animals have made a significant gene breakthrough identifying the components of the p16p16INK4a/Rb pathway as the principal and rate-limiting targets of UV radiation actions in melanoma formation. This review summarizes the current knowledge of the molecular mechanisms involved in melanoma development and its relationship to sunlight UV radiation.

scholarly journals FLYWCH1, a Multi-Functional Zinc Finger Protein Contributes to the DNA Repair Pathway

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 889
Author(s):  
Sheema Almozyan ◽  
James Coulton ◽  
Roya Babaei-Jadidi ◽  
Abdolrahman S. Nateri
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Zinc Finger ◽  
Dna Damage Response ◽  
Zinc Finger Protein ◽  
Uv Light ◽  
Potential Contribution ◽  
Dna Damage And Repair ◽  
Endogenous Expression ◽  
Damage Response

Over recent years, several Cys2-His2 (C2H2) domain-containing proteins have emerged as critical players in repairing DNA-double strand breaks. Human FLYWCH1 is a newly characterised nuclear transcription factor with (C2H2)-type zinc-finger DNA-binding domains. Yet, our knowledge about FLYWCH1 is still in its infancy. This study explores the expression, role and regulation of FLYWCH1 in the context of DNA damage and repair. We provide evidence suggesting a potential contribution of FLYWCH1 in facilitating the recruitment of DNA-damage response proteins (DDRPs). We found that FLYWCH1 colocalises with γH2AX in normal fibroblasts and colorectal cancer (CRC) cell lines. Importantly, our results showed that enforced expression of FLYWCH1 induces the expression of γH2AX, ATM and P53 proteins. Using an ATM-knockout (ATMKO) model, we indicated that FLYWCH1 mediates the phosphorylation of H2AX (Ser139) independently to ATM expression. On the other hand, the induction of DNA damage using UV-light induces the endogenous expression of FLYWCH1. Conversely, cisplatin treatment reduces the endogenous level of FLYWCH1 in CRC cell lines. Together, our findings uncover a novel FLYWCH1/H2AX phosphorylation axis in steady-state conditions and during the induction of the DNA-damage response (DDR). Although the role of FLYWCH1 within the DDR machinery remains largely uncharacterised and poorly understood, we here report for the first-time findings that implicate FLYWCH1 as a potential participant in the DNA damage response signaling pathways.

scholarly journals Deletion of Mouse Rad9 Causes Abnormal Cellular Responses to DNA Damage, Genomic Instability, and Embryonic Lethality

2004 ◽  
Vol 24 (16) ◽  
pp. 7235-7248 ◽  
Author(s):  
Kevin M. Hopkins ◽  
Wojtek Auerbach ◽  
Xiang Yuan Wang ◽  
M. Prakash Hande ◽  
Haiying Hang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cellular Response ◽  
Gamma Ray ◽  
Uv Light ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Cell Cycle Checkpoints ◽  
Genomic Integrity ◽  
Targeted Deletion ◽  
Spontaneous Chromosome

ABSTRACT The fission yeast Schizosaccharomyces pombe rad9 gene promotes cell survival through activation of cell cycle checkpoints induced by DNA damage. Mouse embryonic stem cells with a targeted deletion of Mrad9, the mouse ortholog of this gene, were created to evaluate its function in mammals. Mrad9 −/− cells demonstrated a marked increase in spontaneous chromosome aberrations and HPRT mutations, indicating a role in the maintenance of genomic integrity. These cells were also extremely sensitive to UV light, gamma rays, and hydroxyurea, and heterozygotes were somewhat sensitive to the last two agents relative to Mrad9 +/+ controls. Mrad9 −/− cells could initiate but not maintain gamma-ray-induced G2 delay and retained the ability to delay DNA synthesis rapidly after UV irradiation, suggesting that checkpoint abnormalities contribute little to the radiosensitivity observed. Ectopic expression of Mrad9 or human HRAD9 complemented Mrad9 −/− cell defects, indicating that the gene has radioresponse and genomic maintenance functions that are evolutionarily conserved. Mrad9 +/− mice were generated, but heterozygous intercrosses failed to yield Mrad9 −/− pups, since embryos died at midgestation. Furthermore, Mrad9 −/− mouse embryo fibroblasts were not viable. These investigations establish Mrad9 as a key mammalian genetic element of pathways that regulate the cellular response to DNA damage, maintenance of genomic integrity, and proper embryonic development.

scholarly journals Advances in DNA Repair—Emerging Players in the Arena of Eukaryotic DNA Repair

2020 ◽  
Vol 21 (11) ◽  
pp. 3934
Author(s):  
Mateusz Kciuk ◽  
Karol Bukowski ◽  
Beata Marciniak ◽  
Renata Kontek
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Damage Response ◽  
Current Knowledge ◽  
New Agents ◽  
Dna Damage And Repair ◽  
Damage Response ◽  
Eukaryotic Dna ◽  
Shock Proteins ◽  
Review Current

Genomic DNA is constantly damaged by factors produced during natural metabolic processes as well as agents coming from the external environment. Considering such a wide array of damaging agents, eukaryotic cells have evolved a DNA damage response (DRR) that opposes the influence of deleterious factors. Despite the broad knowledge regarding DNA damage and repair, new areas of research are emerging. New players in the field of DDR are constantly being discovered. The aim of this study is to review current knowledge regarding the roles of sirtuins, heat shock proteins, long-noncoding RNAs and the circadian clock in DDR and distinguish new agents that may have a prominent role in DNA damage response and repair.

scholarly journals DNA damage and repair kinetics after microbeam radiation therapy emulation in living cells using monoenergetic synchrotron X-ray microbeams

2011 ◽  
Vol 18 (4) ◽  
pp. 630-636 ◽  
Author(s):  
Carl N. Sprung ◽  
Marian Cholewa ◽  
Noriko Usami ◽  
Katsumi Kobayashi ◽  
Jeffrey C. Crosbie
Keyword(s):  
Dna Damage ◽  
Radiation Therapy ◽  
Cellular Response ◽  
Time Frame ◽  
X Rays ◽  
Bystander Effects ◽  
Dna Damage And Repair ◽  
Tumour Control ◽  
Microbeam Radiation Therapy ◽  
Γh2ax Foci

A novel synchrotron-based approach, known as microbeam radiation therapy (MRT), currently shows considerable promise in increased tumour control and reduced normal tissue damage compared with conventional radiotherapy. Different microbeam widths and separations were investigated using a controlled cell culture system and monoenergetic (5.35 keV) synchrotron X-rays in order to gain further insight into the underlying cellular response to MRT. DNA damage and repair was measured using fluorescent antibodies against phosphorylated histone H2AX, which also allowed us to verify the exact location of the microbeam path. Beam dimensions that reproduced promising MRT strategies were used to identify useful methods to study the underpinnings of MRT. These studies include the investigation of different spatial configurations on bystander effects. γH2AX foci number were robustly induced in directly hit cells and considerable DNA double-strand break repair occurred by 12 h post-10 Gy irradiation; however, many cells had some γH2AX foci at the 12 h time point. γH2AX foci at later time points did not directly correspond with the targeted regions suggesting cell movement or bystander effects as a potential mechanism for MRT effectiveness. Partial irradiation of single nuclei was also investigated and in most cases γH2AX foci were not observed outside the field of irradiation within 1 h after irradiation indicating very little chromatin movement in this time frame. These studies contribute to the understanding of the fundamental radiation biology relating to the MRT response, a potential new therapy for cancer patients.

scholarly journals MicroRNAs Involvement in Radioresistance of Head and Neck Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Parwez Ahmad ◽  
Jiri Sana ◽  
Marek Slavik ◽  
Pavel Slampa ◽  
Pavel Smilek ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Special Focus ◽  
Specific Expression ◽  
Dna Damage And Repair ◽  
Rna Molecules

Resistance to the ionizing radiation is a current problem in the treatment and clinical management of various cancers including head and neck cancer. There are several biological and molecular mechanisms described to be responsible for resistance of the tumors to radiotherapy. Among them, the main mechanisms include alterations in intracellular pathways involved in DNA damage and repair, apoptosis, proliferation, and angiogenesis. It has been found that regulation of these complex processes is often controlled by microRNAs. MicroRNAs are short endogenous RNA molecules that posttranscriptionally modulate gene expression and their deregulated expression has been observed in many tumors including head and neck cancer. Specific expression patterns of microRNAs have also been shown to predict prognosis and therapeutic response in head and neck cancer. Therefore, microRNAs present promising biomarkers and therapeutic targets that might overcome resistance to radiation and improve prognosis of head and neck cancer patients. In this review, we summarize the current knowledge of the functional role of microRNAs in radioresistance of cancer with special focus on head and neck cancer.

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