uv-induced dna damage and repair a review pdf lite

Uv-induced dna damage and repair a review pdf lite

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Introduction

Apple Flavonoids Suppress Carcinogen-Induced DNA Damage in Normal Human Bronchial Epithelial Cells

Antioxidants and Cancer: Theories, Techniques, and Trials in Preventing Cancer

Qingyi Wei, Jeffrey E. Lee, Jeffrey E. Gershenwald, Merrick I.

UV light targets both membrane receptors and nuclear DNA, thus evoking signals triggering apoptosis. Although receptor-mediated apoptosis has been extensively investigated, the role of DNA damage in apoptosis is less clear. NER-deficient cells were hypersensitive as to the induction of apoptosis, indicating that apoptosis induced by UV-C light is due to unrepaired DNA base damage. Unrepaired lesions, however, do not activate the apoptotic pathway directly because apoptosis upon UV-C irradiation requires DNA replication and cell proliferation. It is also shown that in NER-deficient cells unrepaired lesions are converted into DNA double-strand breaks DSBs and chromosomal aberrations by a replication-dependent process that precedes apoptosis.

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Purpose : The purpose of this study was to investigate the mechanisms by which miR may contribute to the phenotypic alterations associated with stress-induced senescence of human trabecular meshwork HTM cells. Conclusions : Our results suggest that the observed up-regulation of miR after stress-induced senescence in HTM cells may contribute to reinforce cellular senescence by inhibiting cell cycle progression through multiple gene targets and limiting the DNA repair mechanisms through inhibition of KIAA Purchase this article with an account.

Jump To Open Access. Alerts User Alerts. You will receive an email whenever this article is corrected, updated, or cited in the literature. You can manage this and all other alerts in My Account. This feature is available to authenticated users only. Get Citation Citation. Get Permissions. Senescent cells display phenotypic alterations that could contribute to disruption of tissue homeostasis in aging.

Although miR has been reported to promote cell and tumor growth, 22 — 24 there is also evidence for a role of miR as an inhibitor of cell proliferation and cancer growth. Although down-regulation of miR inhibits apoptosis and enhances cell survival of endometrial stromal cells in endometriosis, 34 up-regulation of miR has been reported to inhibit TGF-beta 1—induced apoptosis by down-regulation of PDCD4 expression in human hepatocellular carcinoma cells.

In order to gain a better understanding of the biological roles of miR and its contribution to the senescent phenotype of HTM cells, we analyzed by gene array the effects of miR over-expression on the gene expression profile of HTM cells, validated experimentally four novel targets and conducted functional analysis of the effects on cell proliferation and ultra violet UV induced DNA damage repair mediated by targeting of the recently identified target KIAA 32 by miR in HTMs.

Human tissue for generation of trabecular meshwork cell cultures was obtained from the Eye Bank for Sight Restoration, Inc. Three days after transfection, HTM cells were harvested by adding lysis buffer from the kit and homogenization using a QIAshredder spin column Qiagen. This array covers the Human Genome U Set plus additional genes for analysis of more than 47, transcripts.

Genes were filtered to their intensities in the control channel. The fluorescence threshold value C t was calculated using the iCycle system software Bio-Rad. The specific primer pairs used were listed in Table 1. Cultured cells were washed twice in cold phosphate-buffered saline PBS.

For detection of endogenous control, the membrane was stripped with stripping buffer 25 mM glycine, pH 3. The fragment amplified by this primer pair was cloned into pCR2. The fragment was then ligated to pcDNA3.

An empty pcDNA3. The color was then developed by adding Substrate Solution to each well. After 15 minutes of incubation in the dark at room temperature, Stop Solution was added to each well, and absorbance was measured using a spectrophotometric plate reader at dual wavelengths of to nm. The slides were then subjected to TBE electrophoresis for 10 minutes. The image was visualized and captured using fluorescence microscopy. Statistical significance between groups was assessed by the Mann-Whitney U test.

Three days after transfection, RNAs were extracted, and Affymetrix gene array was conducted. Results were analyzed using GeneSpring version 10 software Agilent , which indicated that genes were significantly 2-fold up- or down-regulated more than by miR Supplementary Table S1. Pathway analysis indicated strong involvement of miR in the regulation of cell cycle progression and DNA damage response Fig.

As shown in Table 2 , 25 of these genes showed consistent and significant up- or down-regulation in all 3 HTM cell lines. Figure 1. View Original Download Slide. MetaCore pathway analysis of the Affymetrix gene array. GeneGo pathways were identified by MetaCore analysis as the most significantly affected by miR Cell cycle and its regulation were the highest ranking in terms of P value and Gene Ontology interpretation.

Figure 2. Figure 3. Figure 4. KIAA partially mediated the effects on cell proliferation induced by miR Cells were then fixed, and proliferation was determined by using BrdU cell proliferation assay kit. Figure 5. Two hours after UV irradiation, cells were collected, and DNA damage was determined using CometAssay kit for single-cell gel electrophoresis assay. Quantitative data were generated by image analysis of the length of the comet tail from 75 to random individual cells for each group.

These results suggested that targeting of KIAA could potentially play an important role on the biological effects mediated by miR Although miR also inhibited cell proliferation in HDFs at levels similar to those in HTM cells, the rescue of this effect by KIAA was only partial, suggesting that other targets are likely to contribute to the inhibition of cell growth in these cells.

In contrast to the study by Roche et al. However, we evaluated cell proliferation by BrdU incorporation only 24 hours after transfection with miR, whereas Roche et al.

Therefore, differences in methodology may account for this discrepancy. In any case, our results indicate that inhibitory effects of miR on proliferation may be cell type dependent, and are only partially dependent on the targeting of KIAA Our results demonstrated that expression of miR leads to increased susceptibility to UV-induced DNA damage and that this effect could be completely abolished by restoring expression of KIAA These genes can also potentially contribute to functional effects of miR on cell cycle and DNA repair.

PLK1 has multiple important roles in cell cycle progression and in cellular response to DNA damage 40 — 43 ; it strongly promotes progression of the cell cycle and is responsible for aggressive proliferation of tumor cells 44 ; and its over-expression enables cells to override checkpoints, leading to genomic instability and promoting cell transformation. While siRNA-mediated inhibition of presenilin 2 inhibits glioma cell growth and invasion, 52 similar inhibition by siRNA has been demonstrated to increased lung cancer cell growth.

However, the role this miRNA in the regulation of cell cycle and its potential contribution to reinforce the senescent phenotype may be cell type specific and also the consequence of the combined effects of multiple target genes. Further studies aimed at a more complete identification and functional analysis of miR targets will be necessary to better understand the physiologic role of miR Inhibition of cell proliferation by miR appears to be only partially mediated by targeting of KIAA Overall, these results are consistent with a role for miR in reinforcing cellular senescence by inhibiting cell cycle progression, and at the same time limiting the DNA repair mechanisms, which could lead to increase rate of mutations.

Disclosure: G. Li , None; C. Luna , None; P. Gonzalez , None. Campisi J. Aging, cellular senescence, and cancer. Ann Rev Physiol. Ohtani N, Hara E. Roles and mechanisms of cellular senescence in regulation of tissue homeostasis. Cancer Sci. Genome-wide expression profile of human trabecular meshwork cultured cells nonglaucomatous and primary open angle glaucoma tissue. Mol Vis.

Sacca SC, Izzotti A. Oxidative stress and glaucoma: injury in the anterior segment of the eye. Prog Brain Res. The intrinsic stiffness of human trabecular meshwork cells increases with senescence. Oxidative damage and autophagy in the human trabecular meshwork as related with ageing. PLoS One. Senescent phenotype of trabecular meshwork cells displays biomarkers in primary open-angle glaucoma.

Curr Mol Med. Invest Ophthalmol Vis Sci. Alterations in microRNA expression in stress-induced cellular senescence. Mech Ageing Dev. Targeting of integrin beta1 and kinesin 2alpha by microRNA J Biol Chem. MicroRNA family members regulate sensorineural fates in the inner ear. J Neurosci. Li H, Fekete DM. MicroRNAs in hair cell development and deafness. MiR family regulates chloride intracellular channel 5 expression in inner ear hair cells. Toxicol In Vitro. Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.

MicroRNA family conservation and ciliated neurosensory organ expression. Evol Dev. Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa. Genome Biol. Eur Urol.

Introduction

Ambient ultraviolet-B UVB radiation induces lethal effects in the two-spotted spider mite Tetranychus urticae , whereas photoreactivation by irradiation with ultraviolet-A and visible light VIS plays an important role to increase survival of mites irradiated by UVB. The physiological mechanisms and ecological significance of photoreactivation in terrestrial arthropods have not been shown clearly. Instead, expression of xeroderma pigmentosum A XPA was increased by irradiation. XPA is a core factor in nucleotide excision repair NER , which is a repair system unrelated to photo energy. The relationship between gene expression and enzymatic repair remains unclear. To elucidate the PER process in T. In fact, humans do not possess photolyase Li et al.

This page has been archived and is no longer updated. In addition to genetic insults caused by the environment, the very process of DNA replication during cell division is prone to error. The rate at which DNA polymerase adds incorrect nucleotides during DNA replication is a major factor in determining the spontaneous mutation rate in an organism. While a " proofreading " enzyme normally recognizes and corrects many of these errors, some mutations survive this process. Estimates of the frequency at which human DNA undergoes lasting, uncorrected errors range from 1 x 10 -4 to 1 x 10 -6 mutations per gamete for a given gene.

Apple Flavonoids Suppress Carcinogen-Induced DNA Damage in Normal Human Bronchial Epithelial Cells

Human skin is continuously exposed to environmental DNA damage leading to the accumulation of somatic mutations over the lifetime of an individual. The contributions of these processes to the somatic mutation load in the skin of healthy humans has so far not been accurately assessed because the low numbers of mutations from current sequencing methodologies preclude the distinction between sequencing errors and true somatic genome changes. In this work, we sequenced genomes of single cell-derived clonal lineages obtained from primary skin cells of a large cohort of healthy individuals across a wide range of ages.

DNA Damage & Repair: Mechanisms for Maintaining DNA Integrity

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Antioxidants and Cancer: Theories, Techniques, and Trials in Preventing Cancer

Purpose : The purpose of this study was to investigate the mechanisms by which miR may contribute to the phenotypic alterations associated with stress-induced senescence of human trabecular meshwork HTM cells. Conclusions : Our results suggest that the observed up-regulation of miR after stress-induced senescence in HTM cells may contribute to reinforce cellular senescence by inhibiting cell cycle progression through multiple gene targets and limiting the DNA repair mechanisms through inhibition of KIAA Purchase this article with an account. Jump To Open Access.

DNA repair diseases: what do they tell us about cancer and aging? Send correspondence to. The discovery of DNA repair defects in human syndromes, initially in xeroderma pigmentosum XP but later in many others, led to striking observations on the association of molecular defects and patients' clinical phenotypes.

Участники движения за гражданские свободы торжествовали и настаивали на том, что АНБ ни при каких обстоятельствах не должно читать их почту. Программы компьютерного кодирования раскупались как горячие пирожки.

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Женщина с кровотечением… плачущая молодая пара… молящаяся маленькая девочка. Наконец Беккер дошел до конца темного коридора и толкнул чуть приоткрытую дверь слева. Комната была пуста, если не считать старой изможденной женщины на койке, пытавшейся подсунуть под себя судно. Хорошенькое зрелище, - подумал Беккер.  - Где, черт возьми, регистратура. За едва заметным изгибом коридора Беккер услышал голоса.

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