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DNA damage response

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https://www.readbyqxmd.com/read/28647894/keratin-gene-mutations-influence-the-keratinocyte-response-to-dna-damage-and-cytokine-induced-apoptosis
#1
Tina Zupancic, Gregor Sersa, Hans Törmä, Ellen Birgitte Lane, Harald Herrmann, Radovan Komel, Mirjana Liovic
The keratin filament cytoskeleton is vital to the normal function of epithelial cells. It provides structural support and regulates different aspects of cell metabolism. Mutations in keratins 5 and 14 cause a skin fragility disorder, epidermolysis bullosa simplex (EBS). Patients with severe EBS have an increased cumulative risk for basal cell carcinoma. In this study, we tested how keratin 5 and 14 mutant EBS patient-derived keratinocytes behave in the face of two different types of stressors that are able to induce cell death: ionizing radiation and cytokines TNF-α and TRAIL...
June 24, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28647496/a-comprehensive-complex-systems-approach-to-the-study-and-analysis-of-mammalian-cell-cycle-control-system-in-the-presence-of-dna-damage-stress
#2
Ali Abroudi, Sandhya Samarasinghe, Don Kulasiri
Not many models of mammalian cell cycle system exist due to its complexity. Some models are too complex and hard to understand, while some others are too simple and not comprehensive enough. Moreover, some essential aspects, such as the response of G1-S and G2-M checkpoints to DNA damage as well as the growth factor signalling, have not been investigated from a systems point of view in current mammalian cell cycle models. To address these issues, we bring a holistic perspective to cell cycle by mathematically modelling it as a complex system consisting of important sub-systems that interact with each other...
June 21, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28646271/characterization-of-adipose-derived-stem-cells-following-burn-injury
#3
Anesh Prasai, Amina El Ayadi, Randy C Mifflin, Michael D Wetzel, Clark R Andersen, Heinz Redl, David N Herndon, Celeste C Finnerty
Severe burns induce a prolonged inflammatory response in subcutaneous adipose tissue that modulates signaling in adipose-derived stem cells (ASCs), which hold potential for healing burn wounds or generating skin substitutes. Using a 60% rat scald burn model, we conducted a series of experiments to determine which cells isolated from the adipose tissue produced inflammatory mediators and how these changes affect ASC fate and function. The stromal vascular fraction (SVF), adipocytes, and ASCs were isolated from adipose tissue at varying times up to 4 weeks postburn and from non-injured controls...
June 23, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28646234/electroporation-as-a-vaccine-delivery-system-and-a-natural-adjuvant-to-intradermal-administration-of-plasmid-dna-in-macaques
#4
Biliana Todorova, Lucille Adam, Slobodan Culina, Raphaël Boisgard, Frédéric Martinon, Antonio Cosma, Mart Ustav, Thierry Kortulewski, Roger Le Grand, Catherine Chapon
In vivo electroporation (EP) is used to enhance the uptake of nucleic acids and its association with DNA vaccination greatly stimulates immune responses to vaccine antigens delivered through the skin. However, the effect of EP on cutaneous cell behavior, the dynamics of immune cell recruitment and local inflammatory factors, have not been fully described. Here, we show that intradermal DNA vaccination combined with EP extends antigen expression to the epidermis and the subcutaneous skin muscle in non-human primates...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646223/regular-exercise-participation-improves-genomic-stability-in-diabetic-patients-an-exploratory-study-to-analyse-telomere-length-and-dna-damage
#5
Ivan Dimauro, Antonella Sgura, Monica Pittaluga, Fiorenza Magi, Cristina Fantini, Rosa Mancinelli, Antonio Sgadari, Stefania Fulle, Daniela Caporossi
Physical activity has been demonstrated to be effective in the prevention and treatment of different chronic conditions, including type 2 diabetes (T2D). In particular, several studies highlighted how the beneficial effects of physical activity may be related to the stability of the DNA molecule, such as longer telomeric ends. Here we analyze the effect of exercise training on telomere length, spontaneous and H2O2-induced DNA damage, as well as the apoptosis level in leukocytes from untrained or trained T2D patients vs...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646114/staphylococcus-aureus-strain-newman-photoinactivation-and-cellular-response-to-sunlight-exposure
#6
Jill S McClary, Lauren M Sassoubre, Alexandria B Boehm
Sunlight influences microbial water quality of surface waters. Previous studies have investigated photoinactivation mechanisms and cellular photostress responses of fecal indicator bacteria (FIB), including Escherichia coli and enterococci, but further work is needed to characterize photostress responses of bacterial pathogens. Here we investigate the photoinactivation of Staphylococcus aureus (strain Newman), a pigmented, waterborne pathogen of emerging concern. We measured photodecay using standard culture-based assays and cellular membrane integrity; and investigated photostress response by measuring the relative number of mRNA transcripts of select oxidative stress, DNA repair, and metabolism genes...
June 23, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28645370/xenopus-laevis-as-model-system-to-study-dna-damage-response-and-replication-fork-stability
#7
Vincenzo Sannino, Federica Pezzimenti, Stefania Bertora, Vincenzo Costanzo
Although many players of the DNA damage response and DNA repair have been identified in several systems their biochemical role is still poorly understood. The use of the Xenopus laevis egg extract cell-free system allowed biochemical dissection of DNA replication and cell cycle events in a complex biological context. The possibility of manipulating the protein content by using protein depletion procedures makes egg extract a powerful system to study proteins whose inactivation results in cellular lethality...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28645083/graphene-oxide-nanosheets-induce-dna-damage-and-activate-the-base-excision-repair-ber-signaling-pathway-both-in%C3%A2-vitro-and-in%C3%A2-vivo
#8
Chun-Jiao Lu, Xue-Feng Jiang, Muhammad Junaid, Yan-Bo Ma, Pan-Pan Jia, Hua-Bin Wang, De-Sheng Pei
Graphene oxide (GO) has widespread concerns in the fields of biological sciences and medical applications. Currently, studies have reported that excessive GO exposure can cause cellular DNA damage through reactive oxygen species (ROS) generation. However, DNA damage mediated response of the base excision repair (BER) pathway due to GO exposure is not elucidated yet. Therefore, we exposed HEK293T cells and zebrafish embryos to different concentrations of GO for 24 h, and transcriptional profiles of BER pathway genes, DNA damage, and cell viability were analyzed both in vitro and in vivo...
June 14, 2017: Chemosphere
https://www.readbyqxmd.com/read/28644990/global-transcriptional-response-of-escherichia-coli-mg1655-cells-exposed-to-the-oxygenated-monoterpenes-citral-and-carvacrol
#9
Beatriz Chueca, Elisa Pérez-Sáez, Rafael Pagán, Diego García-Gonzalo
DNA microarrays were used to study the mechanism of bacterial inactivation by carvacrol and citral. After 10-min treatments of Escherichia coli MG1655 cells with 100 and 50ppm of carvacrol and citral, 76 and 156 genes demonstrated significant transcriptional differences (p≤0.05), respectively. Among the up-regulated genes after carvacrol treatment, we found gene coding for multidrug efflux pumps (acrA, mdtM), genes related to phage shock response (pspA, pspB, pspC, pspD, pspF and pspG), biosynthesis of arginine (argC, argG, artJ), and purine nucleotides (purC, purM)...
June 20, 2017: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/28644387/rna-binding-proteins-and-genome-integrity
#10
REVIEW
Kensei Nishida, Yuki Kuwano, Tatsuya Nishikawa, Kiyoshi Masuda, Kazuhito Rokutan
Genome integrity can be threatened by various endogenous or exogenous events. To counteract these stressors, the DNA damage response network contributes to the prevention and/or repair of genomic DNA damage and serves an essential function in cellular survival. DNA binding proteins are involved in this network. Recently, several RNA-binding proteins (RBPs) that are recruited to DNA damage sites have been shown to be direct players in the prevention or repair of DNA damage. In addition, non-coding RNAs, themselves, are involved in the RNA-mediated DNA repair system...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28643452/emerging-nanotechnology-and-advanced-materials-for-cancer-radiation-therapy
#11
REVIEW
Guosheng Song, Liang Cheng, Yu Chao, Kai Yang, Zhuang Liu
Radiation therapy (RT) including external beam radiotherapy (EBRT) and internal radioisotope therapy (RIT) has been widely used for clinical cancer treatment. However, owing to the low radiation absorption of tumors, high doses of ionizing radiations are often needed during RT, leading to severe damages to normal tissues adjacent to tumors. Meanwhile, the RT efficacies are limited by different mechanisms, among which the tumor hypoxia-associated radiation resistance is a well-known one, as there exists hypoxia inside most solid tumors while oxygen is essential to enhance radiation-induced DNA damages...
June 23, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28642865/spinal-muscular-atrophy-from-defective-chaperoning-of-snrnp-assembly-to-neuromuscular-dysfunction
#12
REVIEW
Maia Lanfranco, Neville Vassallo, Ruben J Cauchi
Spinal Muscular Atrophy (SMA) is a neuromuscular disorder that results from decreased levels of the survival motor neuron (SMN) protein. SMN is part of a multiprotein complex that also includes Gemins 2-8 and Unrip. The SMN-Gemins complex cooperates with the protein arginine methyltransferase 5 (PRMT5) complex, whose constituents include WD45, PRMT5 and pICln. Both complexes function as molecular chaperones, interacting with and assisting in the assembly of an Sm protein core onto small nuclear RNAs (snRNAs) to generate small nuclear ribonucleoproteins (snRNPs), which are the operating components of the spliceosome...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28642487/hypoxia-is-a-key-driver-of-alternative-splicing-in-human-breast-cancer-cells
#13
Jian Han, Jia Li, Jolene Caifeng Ho, Grace Sushin Chia, Hiroyuki Kato, Sudhakar Jha, Henry Yang, Lorenz Poellinger, Kian Leong Lee
Adaptation to hypoxia, a hallmark feature of many tumors, is an important driver of cancer cell survival, proliferation and the development of resistance to chemotherapy. Hypoxia-induced stabilization of hypoxia-inducible factors (HIFs) leads to transcriptional activation of a network of hypoxia target genes involved in angiogenesis, cell growth, glycolysis, DNA damage repair and apoptosis. Although the transcriptional targets of hypoxia have been characterized, the alternative splicing of transcripts that occurs during hypoxia and the roles they play in oncogenesis are much less understood...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642363/nuclear-phosphorylated-dicer-processes-double-stranded-rna-in-response-to-dna-damage
#14
Kaspar Burger, Margarita Schlackow, Martin Potts, Svenja Hester, Shabaz Mohammed, Monika Gullerova
The endoribonuclease Dicer is a key component of the human RNA interference pathway and is known for its role in cytoplasmic microRNA production. Recent findings suggest that noncanonical Dicer generates small noncoding RNA to mediate the DNA damage response (DDR). Here, we show that human Dicer is phosphorylated in the platform-Piwi/Argonaute/Zwille-connector helix cassette (S1016) upon induction of DNA damage. Phosphorylated Dicer (p-Dicer) accumulates in the nucleus and is recruited to DNA double-strand breaks...
June 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28641940/dormant-origins-as-a-built-in-safeguard-in-eukaryotic-dna-replication-against-genome-instability-and-disease-development
#15
REVIEW
Naoko Shima, Kayla D Pederson
DNA replication is a prerequisite for cell proliferation, yet it can be increasingly challenging for a eukaryotic cell to faithfully duplicate its genome as its size and complexity expands. Dormant origins now emerge as a key component for cells to successfully accomplish such a demanding but essential task. In this perspective, we will first provide an overview of the fundamental processes eukaryotic cells have developed to regulate origin licensing and firing. With a special focus on mammalian systems, we will then highlight the role of dormant origins in preventing replication-associated genome instability and their functional interplay with proteins involved in the DNA damage repair response for tumor suppression...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28641873/targeting-dna-repair-for-precision-radiotherapy-balancing-the-therapeutic-ratio
#16
REVIEW
Osman Mahamud, Jonathan So, Melvin L K Chua, Robert G Bristow
Genomic instability is underpinned by defects in the DNA damage response and DNA repair pathways. Subsequent clonal selection and adaption can lead to a mutator phenotype and tumor aggression. Importantly, tumor cell sensitivity to chemotherapy and radiotherapy can depend highly on the cellular capacity to repair DNA damage within and between tumor types. Annotation of functional defects in DNA damage response and DNA repair function may allow for the development of novel prognostic biomarkers. This information could also be used to predict therapeutic response, including predicting responses following inhibition of DNA repair...
April 25, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28641368/glomerular-hyperfiltration-in-obese-african-american-hypertensive-patients-is-associated-with-elevated-urinary-mitochondrial-dna-copy-number
#17
Alfonso Eirin, Ahmed Saad, John R Woollard, Luis A Juncos, David A Calhoun, Hui Tang, Amir Lerman, Stephen C Textor, Lilach O Lerman
BACKGROUND: Glomerular hyperfiltration may contribute to the high incidence of renal disease in Obese African Americans essential hypertensive (ObAAEH) patients, but the precise mechanisms responsible for renal injury have not been elucidated. Mitochondria are important determinants of renal injury in hypertension, and increased levels of mitochondrial DNA (mtDNA) in the urine may indicate renal mitochondrial injury. We hypothesized that urine mtDNA copy numbers would be higher in ObAAEH compared to Caucasian essential hypertensive (CEH) patients...
June 14, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28641314/no-additional-prognostic-value-for-mre11-in-squamous-cell-carcinomas-of-the-anus-treated-with-chemo-radiotherapy
#18
Alexandra K Walker, Christiana Kartsonaki, Elena Collantes, Judith Nicholson, Duncan C Gilbert, Anne E Kiltie
BACKGROUND: The majority of anal cancers (84-95%) are driven by infection with human papillomavirus (HPV). HPV-positive tumours show significantly better responses to chemo-radiotherapy when compared with HPV-negative tumours. HPV infection is linked to alterations in DNA damage response proteins, including MRE11. MRE11 is a potential predictive biomarker for response to radiotherapy in muscle-invasive bladder cancer and may hold predictive power in other cancers. METHODS: Using a previously reported cohort, we evaluated the levels of MRE11 in anal cancer and assessed its predictive value in this disease...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28641178/stimulatory-effect-of-aggregatibacter-actinomycetemcomitans-dna-on-proinflammatory-cytokine-expression-by-human-gingival-fibroblasts
#19
Uriel Soto-Barreras, Gabriela Cortés-Sandoval, Ruben Dominguez-Perez, Alejandra Loyola-Leyva, Panfilo-Raymundo Martinez-Rodriguez, Juan Pablo Loyola-Rodriguez
OBJECTIVE: While different virulence factors have been reported of Aggregatibacter actinomycetemcomitans (Aa), there is little information about the stimulatory effect of its DNA. The main purpose of this study was to assess the inflammatory response of human gingival fibroblasts (HGFs) stimulated with A. actinomycetemcomitans DNA. DESIGN: Cytokine levels of IL-6, IL-1α and TNF-α were measured on the supernatant of HGFs activated with 10, 25, 50 and 100μg/ml DNA of Aa during 24h...
June 15, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28640859/toxic-effects-of-atrazine-on-porcine-oocytes-and-possible-mechanisms-of-action
#20
Bao Yuan, Shuang Liang, Yong-Xun Jin, Ming-Jun Zhang, Jia-Bao Zhang, Nam-Hyung Kim
Because atrazine is a widely used herbicide, its adverse effects on the reproductive system have been extensively researched. In this study, we investigated the effects of atrazine exposure on porcine oocyte maturation and the possible mechanisms. Our results showed that the rates of oocyte maturation significantly decreased after treatment with 200 μM atrazine in vitro. Atrazine treatment resulted in abnormal spindle morphology but did not affect actin distribution. Atrazine exposure not only triggered a DNA damage response but also decreased MPF levels in porcine oocytes...
2017: PloS One
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