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https://www.readbyqxmd.com/read/28392109/compartmentalization-of-dna-damage-response-between-heterochromatin-and-euchromatin-is-mediated-by-distinct-h2a-histone-variants
#1
Zdravko J Lorković, Chulmin Park, Malgorzata Goiser, Danhua Jiang, Marie-Therese Kurzbauer, Peter Schlögelhofer, Frédéric Berger
DNA double-strand break (DSB) repair depends on the ataxia telangiectasia mutated (ATM) kinase that phosphorylates the conserved C-terminal SQ motif present in the histone variant H2A.X [1-7]. In constitutive heterochromatin of mammals, DSB repair is delayed and relies on phosphorylation of the proteins HP1 and KAP1 by ATM [2, 8-14]. However, KAP1 is not conserved in plants and the HP1-related protein Like-HP1 (LHP1) is not localized at constitutive heterochromatin [15], suggesting that in plants, alternative mechanisms could be responsible for repair of DSBs in heterochromatin...
April 5, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28356983/tcn-an-akt-inhibitor-exhibits-potent-antitumor-activity-and-enhances-radiosensitivity-in-hypoxic-esophageal-squamous-cell-carcinoma-in-vitro-and-in-vivo
#2
Qing Guo, Jia He, Feng Shen, Wei Zhang, Xi Yang, Chi Zhang, Qu Zhang, Jun-Xing Huang, Zheng-Dong Wu, Xin-Chen Sun, Sheng-Bin Dai
The aim of the present study was to investigate the radiosensitization effect of triciribine (TCN) on human esophageal squamous cell carcinoma (ESCC) in normoxia or hypoxia and its mechanism. The cytotoxicity and radiosensitization mechanism of TCN were investigated by Cell Counting Kit 8, clonogenic assay, flow cytometry, western blotting (WB) and immunofluorescence staining of phospho-histone H2A.X, Ser139 (γ-H2AX) in ESCC in vitro, while the protein expression levels of AKT, phosphorylated (p)-AKT, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were evaluated by WB in vivo...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28351316/novel-tetrahydroacridine-and-cyclopentaquinoline-derivatives-with-fluorobenzoic-acid-moiety-induce-cell-cycle-arrest-and-apoptosis-in-lung-cancer-cells-by-activation-of-dna-damage-signaling
#3
Paweł Szymański, Paulina Olszewska, Elżbieta Mikiciuk-Olasik, Antoni Różalski, Agnieszka Maszewska, Łukasz Markiewicz, Magda Cuchra, Ireneusz Majsterek
Lung cancer is still the leading cause of cancer-related death worldwide, indicating a necessity to develop more effective therapy. Acridine derivatives are potential anticancer agents due to their ability to intercalate DNA as well as inhibit enzymes involved in replication and transcription. Recently, we have evaluated anticancer activity of 32 novel acridine-based compounds. We found that the most effective were tetrahydroacridine and cyclopentaquinoline derivatives with fluorobenzoic acid containing eight and nine carbon atoms in the aliphatic chain...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28350066/dna-damage-response-defect-in-williams-beuren-syndrome
#4
David Guenat, Giuseppe Merla, Eric Deconinck, Christophe Borg, Pierre-Simon Rohrlich
Williams-Beuren syndrome (WBS, no. OMIM 194050) is a rare multisystem genetic disorder caused by a microdeletion on chromosome 7q11.23 and characterized by cardiovascular malformations, mental retardation, and a specific facial dysmorphism. Recently, we reported that a series of non‑Hodgkin's lymphoma occurs in children with WBS and thus hypothesized that a predisposition to cancer may be associated with this genetic disorder. The aim of the present study was to ascertain the role played by three genes hemizygously deleted in WBS (RFC2, GTF2I and BAZ1B) in DNA damage response pathways...
January 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28316325/silencing-of-the-small-gtpase-diras3-induces-cellular-senescence-in-human-white-adipose-stromal-progenitor-cells
#5
Asim Ejaz, Monika Mattesich, Werner Zwerschke
Inhibition of Akt-mTOR signaling protects from obesity and extends life span in animals. In the present study, we analyse the impact of the small GTPase, GTP-binding RAS-like 3 (DIRAS3), a recently identified weight-loss target gene, on cellular senescence in adipose stromal/progenitor cells (ASCs) derived from human subcutaneous white adipose tissue (sWAT). We demonstrate that DIRAS3 knock-down (KD) in ASCs induces activation of Akt-mTOR signaling and proliferation arrest. DIRAS3 KD ASCs lose the potential to form colonies and are negative for Ki-67...
March 17, 2017: Aging
https://www.readbyqxmd.com/read/28315825/effects-of-florida-red-tides-on-histone-variant-expression-and-dna-methylation-in-the-eastern-oyster-crassostrea-virginica
#6
Rodrigo Gonzalez-Romero, Victoria Suarez-Ulloa, Javier Rodriguez-Casariego, Daniel Garcia-Souto, Gabriel Diaz, Abraham Smith, Juan Jose Pasantes, Gary Rand, Jose M Eirin-Lopez
Massive algal proliferations known as Harmful Algal Blooms (HABs) represent one of the most important threats to coastal areas. Among them, the so-called Florida Red Tides (FRTs, caused by blooms of the dinoflagellate Karenia brevis and associated brevetoxins) are particularly detrimental in the southeastern U.S., causing high mortality rates and annual losses in excess of $40 million. The ability of marine organisms to cope with environmental stressors (including those produced during HABs) is influenced by genetic and epigenetic mechanisms, the latter resulting in phenotypic changes caused by heritable modifications in gene expression, without involving changes in the genetic (DNA) sequence...
March 7, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28284059/reactivating-p53-and-inducing-tumor-apoptosis-rita-enhances-the-response-of-rita-sensitive-colorectal-cancer-cells-to-chemotherapeutic-agents-5-fluorouracil-and-oxaliplatin
#7
Armin Wiegering, Niels Matthes, Bettina Mühling, Monika Koospal, Anne Quenzer, Stephanie Peter, Christoph-Thomas Germer, Michael Linnebacher, Christoph Otto
Colorectal carcinoma (CRC) is the most common cancer of the gastrointestinal tract with frequently dysregulated intracellular signaling pathways, including p53 signaling. The mainstay of chemotherapy treatment of CRC is 5-fluorouracil (5FU) and oxaliplatin. The two anticancer drugs mediate their therapeutic effect via DNA damage-triggered signaling. The small molecule reactivating p53 and inducing tumor apoptosis (RITA) is described as an activator of wild-type and reactivator of mutant p53 function, resulting in elevated levels of p53 protein, cell growth arrest, and cell death...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28270613/smn-deficiency-in-severe-models-of-spinal-muscular-atrophy-causes-widespread-intron-retention-and-dna-damage
#8
Mohini Jangi, Christina Fleet, Patrick Cullen, Shipra V Gupta, Shila Mekhoubad, Eric Chiao, Norm Allaire, C Frank Bennett, Frank Rigo, Adrian R Krainer, Jessica A Hurt, John P Carulli, John F Staropoli
Spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease, is the leading monogenic cause of infant mortality. Homozygous loss of the gene survival of motor neuron 1 (SMN1) causes the selective degeneration of lower motor neurons and subsequent atrophy of proximal skeletal muscles. The SMN1 protein product, survival of motor neuron (SMN), is ubiquitously expressed and is a key factor in the assembly of the core splicing machinery. The molecular mechanisms by which disruption of the broad functions of SMN leads to neurodegeneration remain unclear...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228717/mild-hypothermia-attenuates-the-anesthetic-isoflurane-induced-cytotoxicity
#9
Cheng Li, Yuanlin Dong, Dan Chen, Zhongcong Xie, Yiying Zhang
The commonly used inhalation anesthetic isoflurane has been reported to induce DNA damage and cytotoxicity. However, the methods to attenuate these effects remain largely to be determined. Mild hypothermia has neuroprotective effects. We therefore set out to assess whether mild hypothermia could protect the isoflurane-induced DNA damage and cytotoxicity. Moreover, we investigated the underlying mechanisms by assessing the effects of mild hypothermia on the isoflurane-induced changes in ATP levels. H4 human neuroglioma cells were treated with 2% isoflurane for 3 or 6 h with and without mild hypothermia (35°C)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28213359/methylation-of-the-phosphatase-transcription-activator-eya1-by-protein-arginine-methyltransferase-1-mechanistic-functional-and-structural-studies
#10
Xingguo Li, Allison Eberhardt, Jeanne N Hansen, Dirk Bohmann, Haitao Li, Nina F Schor
The eyes absent (EYA) family proteins are conserved transcriptional coactivators with intrinsic protein phosphatase activity. They play an essential role in the development of various organs in metazoans. These functions are associated with a unique combination of phosphatase and transactivation activities. However, it remains poorly understood how these activities and the consequent biologic functions of EYA are regulated. Here, we demonstrate that 2 conserved arginine residues, R304 and R306, of EYA1 are essential for its in vitro phosphatase activity and in vivo function during Drosophila eye development...
February 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28176872/genotoxic-effects-of-culture-media-on-human-pluripotent-stem-cells
#11
Megha Prakash Bangalore, Syama Adhikarla, Odity Mukherjee, Mitradas M Panicker
Culture conditions play an important role in regulating the genomic integrity of Human Pluripotent Stem Cells (HPSCs). We report that HPSCs cultured in Essential 8 (E8) and mTeSR, two widely used media for feeder-free culturing of HPSCs, had many fold higher levels of ROS and higher mitochondrial potential than cells cultured in Knockout Serum Replacement containing media (KSR). HPSCs also exhibited increased levels of 8-hydroxyguanosine, phospho-histone-H2a.X and p53, as well as increased sensitivity to γ-irradiation in these two media...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28166748/body-mass-index-modifies-the-relationship-between-%C3%AE-h2ax-a-dna-damage-biomarker-and-pathological-complete-response-in-triple-negative-breast-cancer
#12
Maddalena Barba, Patrizia Vici, Laura Pizzuti, Luigi Di Lauro, Domenico Sergi, Anna Di Benedetto, Cristiana Ercolani, Francesca Sperati, Irene Terrenato, Claudio Botti, Lucia Mentuccia, Laura Iezzi, Teresa Gamucci, Clara Natoli, Ilio Vitale, Marcella Mottolese, Ruggero De Maria, Marcello Maugeri-Saccà
BACKGROUND: Body mass index (BMI) is largely investigated as a prognostic and predictive factor in triple-negative breast cancer (TNBC). Overweight and obesity are linked to a variety of pathways regulating tumor-promoting functions, including the DNA damage response (DDR). The DDR physiologically safeguards genome integrity but, in a neoplastic background, it is aberrantly engaged and protects cancer cells from chemotherapy. We herein verified the role of BMI on a previously assessed association between DDR biomarkers and pathological complete response (pCR) in TNBC patients treated with neoadjuvant chemotherapy (NACT)...
February 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28127258/tnf-%C3%AE-sensitizes-chemotherapy-and-radiotherapy-against-breast-cancer-cells
#13
Xiao Wu, Meng-Yao Wu, Min Jiang, Qiaoming Zhi, Xiaojie Bian, Meng-Dan Xu, Fei-Ran Gong, Juan Hou, Min Tao, Liu-Mei Shou, Weiming Duan, Kai Chen, Meng Shen, Wei Li
PURPOSE: Despite new developments in cancer therapy, chemotherapy and radiotherapy remain the cornerstone of breast cancer treatment. Therefore, finding ways to reduce the toxicity and increase sensitivity is particularly important. Tumor necrosis factor alpha (TNF-α) exerts multiple functions in cell proliferation, differentiation and apoptosis. In the present study, we investigated whether TNF-α could enhance the effect of chemotherapy and radiotherapy against breast cancer cells...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28098861/triptolide-inhibits-viability-and-induces-apoptosis-in-liver-cancer-cells-through-activation-of-the-tumor-suppressor-gene-p53
#14
Yan-Yan Sun, Lei Xiao, Dong Wang, Yan-Chao Ji, Yu-Peng Yang, Rong Ma, Xi-Hai Chen
The present study investigated the effect of triptolide on viability and apoptosis along with underlying mechanism in liver cancer cells. CCK-8 assay showed that triptolide treatment for 48 h significantly reduced the viability of HepG2 and QSG7701 cells at 50 µM concentration. Annexin V-FITC and propidium iodide staining showed that triptolide treatment of HepG2 cells at 50 µM concentrations induced apoptosis in 56.45% cells compared to only 2.36% cells in the control cultures. Western blot assay showed that treatment of HepG2 cells with 50 µM concentration of triptolide significantly induced phosphorylation of p53 in a 2 h-treatment...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28098859/dna-damage-response-defect-in-williams-beuren-syndrome
#15
David Guenat, Giuseppe Merla, Eric Deconinck, Christophe Borg, Pierre-Simon Rohrlich
Williams-Beuren syndrome (WBS, no. OMIM 194050) is a rare multisystem genetic disorder caused by a microdeletion on chromosome 7q11.23 and characterized by cardiovascular malformations, mental retardation, and a specific facial dysmorphism. Recently, we reported that a series of non‑Hodgkin's lymphoma occurs in children with WBS and thus hypothesized that a predisposition to cancer may be associated with this genetic disorder. The aim of the present study was to ascertain the role played by three genes hemizygously deleted in WBS (RFC2, GTF2I and BAZ1B) in DNA damage response pathways...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28038734/partially-assembled-nucleosome-structures-at%C3%A2-atomic-detail
#16
Georgy N Rychkov, Andrey V Ilatovskiy, Igor B Nazarov, Alexey V Shvetsov, Dmitry V Lebedev, Alexander Y Konev, Vladimir V Isaev-Ivanov, Alexey V Onufriev
The evidence is now overwhelming that partially assembled nucleosome states (PANS) are as important as the canonical nucleosome structure for the understanding of how accessibility to genomic DNA is regulated in cells. We use a combination of molecular dynamics simulation and atomic force microscopy to deliver, in atomic detail, structural models of three key PANS: the hexasome (H2A·H2B)·(H3·H4)2, the tetrasome (H3·H4)2, and the disome (H3·H4). Despite fluctuations of the conformation of the free DNA in these structures, regions of protected DNA in close contact with the histone core remain stable, thus establishing the basis for the understanding of the role of PANS in DNA accessibility regulation...
February 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28028239/asymmetric-unwrapping-of-nucleosomal-dna-propagates-asymmetric-opening-and-dissociation-of-the-histone-core
#17
Yujie Chen, Joshua M Tokuda, Traci Topping, Steve P Meisburger, Suzette A Pabit, Lisa M Gloss, Lois Pollack
The nucleosome core particle (NCP) is the basic structural unit for genome packaging in eukaryotic cells and consists of DNA wound around a core of eight histone proteins. DNA access is modulated through dynamic processes of NCP disassembly. Partly disassembled structures, such as the hexasome (containing six histones) and the tetrasome (four histones), are important for transcription regulation in vivo. However, the pathways for their formation have been difficult to characterize. We combine time-resolved (TR) small-angle X-ray scattering and TR-FRET to correlate changes in the DNA conformations with composition of the histone core during salt-induced disassembly of canonical NCPs...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27994550/anti-proliferative-and-apoptosis-inducing-effect-of-theabrownin-against-non-small-cell-lung-adenocarcinoma-a549-cells
#18
Feifei Wu, Li Zhou, Wangdong Jin, Weiji Yang, Ying Wang, Bo Yan, Wenlin Du, Qiang Zhang, Lei Zhang, Yonghua Guo, Jin Zhang, Letian Shan, Thomas Efferth
With the highest cancer incidence rate, lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer death in the world. Tea (leaves of Camellia sinensis) has been widely used as a traditional beverage beneficial to human health, including anti-NSCLC activity. Theabrownin (TB) is one major kind of tea pigment responsible for the beneficial effects of tea liquor. However, its effect on NSCLC is unknown. The aim of the present study was to evaluate anti-proliferative and apoptosis-inducing effect of TB on NSCLC (A549) cells, using MTT assay, morphological observation (DAPI staining), in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and annexin-V/PI flow cytometry...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27959435/oridonin-promotes-g2-m-arrest-in-a549-cells-by-facilitating-atm-activation
#19
Mingxing Zheng, Zhibing Zhu, Yongzhao Zhao, Da Yao, Maoqing Wu, Gengyun Sun
Previous studies have demonstrated that oridonin, a tetracyclic diterpenoid compound extracted from Rabdosia rubescens, inhibits proliferation and induces apoptosis in several tumor cell lines. However, the mechanism by which oridonin inhibits the cell cycle remains poorly understood. In the present study, possible mechanisms by which oridonin affects cell cycle progression were explored in A549 lung cancer cells. Flow cytometry analysis indicated that oridonin inhibited the proliferation of A549 cells by inducing G2/M cell cycle arrest in a dose‑dependent manner...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27941214/calcium-alterations-signal-either-to-senescence-or-to-autophagy-induction-in-stem-cells-upon-oxidative-stress
#20
Aleksandra V Borodkina, Alla N Shatrova, Pavel I Deryabin, Anastasiia A Griukova, Polina A Abushik, Sergei M Antonov, Nikolay N Nikolsky, Elena B Burova
Intracellular calcium ([Ca(2+)]i) has been reported to play an important role in autophagy, apoptosis and necrosis, however, a little is known about its impact in senescence. Here we investigated [Ca(2+)]i contribution to oxidative stress-induced senescence of human endometrium-derived stem cells (hMESCs). In hMESCs sublethal H2O2-treatment resulted in a rapid calcium release from intracellular stores mediated by the activation of PLC/IP3/IP3R pathway. Notably, further senescence development was accompanied by persistently elevated [Ca(2+)]i levels...
December 8, 2016: Aging
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