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Antoine Molaro, Janet M Young, Harmit S Malik
Eukaryotic genomes must accomplish both compact packaging for genome stability and inheritance, as well as accessibility for gene expression. They do so using post-translational modifications of four ancient canonical histone proteins (H2A, H2B, H3, and H4) and by deploying histone variants with specialized chromatin functions. Some histone variants are conserved across all eukaryotes, whereas others are lineage-specific. Here, we performed detailed phylogenomic analyses of "short H2A histone" variants found in mammalian genomes...
March 16, 2018: Genome Research
Macarena Guijo, María Ceballos-Chávez, Elena Gómez-Marín, Laura Basurto-Cayuela, José C Reyes
Tudor domain containing protein 9 (TDRD9) is a RNA helicase normally expressed in the germline, where it is involved in the biosynthesis of PIWI-interacting RNAs (piRNAs). Here, we show that TDRD9 is highly expressed in a subset of non-small cell lung carcinomas and derived cell lines by hypomethylation of its CpG island. Furthermore, TDRD9 expression is associated with poor prognosis in lung adenocarcinoma. We find that downregulation of TDRD9 expression in TDRD9-positive cell lines causes a decrease in cell proliferation, S-phase cell cycle arrest, and apoptosis...
February 9, 2018: Oncotarget
David Corujo, Marcus Buschbeck
Histone variants are chromatin components that replace replication-coupled histones in a fraction of nucleosomes and confer particular characteristics to chromatin. H2A variants represent the most numerous and diverse group among histone protein families. In the nucleosomal structure, H2A-H2B dimers can be removed and exchanged more easily than the stable H3-H4 core. The unstructured N-terminal histone tails of all histones, but also the C-terminal tails of H2A histones protrude out of the compact structure of the nucleosome core...
February 27, 2018: Cancers
Thressi Maxwell, Kyu Shik Lee, Soyoung Kim, Kyung-Soo Nam
Arctigenin, a member of the Asteraceae family, is a biologically active lignan that is consumed worldwide due to its several health benefits. However, its use may pose a problem for patients with estrogen receptor (ER)α-positive breast cancer, since studies have shown that arctigenin is a phytoestrogen that exerts a proliferative effect by binding to the ER. Thus, in this study, we examined the effect of arctigenin on ERα-positive MCF-7 human breast cancer cells to determine whether the consumption of arctigenin is safe for patients with breast cancer...
February 9, 2018: International Journal of Oncology
Bing Qiu, Wei Jiang, Wenliang Qiu, Wenling Mu, Yujing Qin, Yongcui Zhu, Jianying Zhang, Qingyi Wang, Dongjie Liu, Zhangyi Qu
Over the last two decades, inducing DNA damage of cancer cells by natural medicines has become a research hotspot in the field of cancer treatment. Although various natural medicines have anticancer effects, very few studies have been conducted to explore the anti-cancer effect of pine needle oil. In the present study, the role of pine needle oil in inducing G2/M arrest in HepG2 cells was investigated. The data revealed that pine needle oil could induce DNA damage in a dose-dependent manner. In the pine needle oil-treated HepG2 cells, the protein levels of phosphorylated (p)-ataxia-telangiectasia mutated (ATM), γ-H2A histone family, member X, p-p53, p-checkpoint kinase 2 and p-cell division cycle 25C were evidently increased, indicating that pine needle oil facilitated G2/M arrest in HepG2 cells through the ATM pathway...
February 2018: Experimental and Therapeutic Medicine
Irina O Vassilieva, Galina F Reshetnikova, Alla N Shatrova, Nataliya V Tsupkina, Marianna V Kharchenko, Larisa L Alekseenko, Nikolay N Nikolsky, Elena B Burova
Accumulating evidence suggests that the senescence-messaging secretome (SMS) factors released by senescent cells play a key role in cellular senescence and physiological aging. Phenomenon of the senescence induction in human endometrium-derived mesenchymal stem cells (MESCs) in response to SMS factors has not yet been described. In present study, we examine a hypothesis whether the conditioned medium from senescent cells (CM-old) may promote premature senescence of young MESCs. In this case, we assume that SMS factors, containing in CM-old are capable to trigger senescence mechanism in a paracrine manner...
January 31, 2018: Biochemical and Biophysical Research Communications
Liza Douiev, Bassam Abu-Libdeh, Ann Saada
In response to Ravera et al. "Fanconi anemia: from DNA repair to metabolism" commenting on our recent publication by Abu-Libdeh, Douiev et al., describing a pathogenic variant in the COX 4I1 gene simulating Fanconi anemia, we wish to add supplementary, pertinent information linking cytochrome c oxidase (COX, mitochondrial respiratory chain complex IV) dysfunction to oxidative stress and nuclear DNA damage. Elevated production of reactive oxygen species (ROS) in COX 4I1 deficient fibroblasts was detected in cells grown in glucose free medium and normalized by ascorbate or N-acetylcysteine supplementation...
February 2, 2018: European Journal of Human Genetics: EJHG
Jiancong Liu, Yang Yu, Suiyi Zhu, Jiakuan Yang, Jian Song, Wei Fan, Hongbin Yu, Dejun Bian, Mingxin Huo
With increasing awareness of reduction of energy and CO2 footprint, more waste is considered recyclable for generating value-added products. Here we reported the negatively-valued iron mud, a waste from groundwater treatment plant, was successfully converted into magnetic adsorbent. Comparing with the conventional calcination method under the high temperature and pressure, the synthesis of the magnetic particles (MPs) by Fe2+/Fe3+ coprecipitation was conducted at environment-friendly condition using ascorbic acid (H2A) as reduction reagent and nitric acid (or acid wastewater) as leaching solution...
2018: PloS One
Ritesh Srivastava, Amie M Traylor, Changzhao Li, Wenguang Feng, Lingling Guo, Veena B Antony, Trenton R Schoeb, Anupam Agarwal, Mohammad Athar
Lewisite (2-chlorovinyldichloroarsine) is an organic and arsenical chemical warfare agent which was developed and weaponized during World Wars I/II. Stockpiles of lewisite still exist in many parts of the world and pose potential environmental and human health threat. Exposure to lewisite and similar chemicals causes intense cutaneous inflammatory response. However, morbidity and mortality in the exposed population is not only due to cutaneous damage but is also a result of systemic injury. Here, we provide data delineating the pathogenesis of acute kidney injury (AKI) following cutaneous exposure to lewisite and its analogue phenylarsine oxide (PAO) in a murine model...
January 17, 2018: American Journal of Physiology. Renal Physiology
Brendan D Hare, Tina M Thornton, Mercedes Rincon, Borivoj Golijanin, S Bradley King, Diane M Jaworski, William A Falls
Recent reports demonstrate that DNA damage is induced, and rapidly repaired, in circuits activated by experience. Moreover, stress hormones are known to slow DNA repair, suggesting that prolonged stress may result in persistent DNA damage. Prolonged stress is known to negatively impact physical and mental health; however, DNA damage as a factor in stress pathology has only begun to be explored. Histone H2A-X phosphorylated at serine 139 (γH2AX) is a marker of DNA double strand breaks (DSB), a type of damage that may lead to cell death if unrepaired...
January 15, 2018: Neuroscience
Valentina Di Nisio, Gianna Rossi, Maria Grazia Palmerini, Guido Macchiarelli, Gian Mario Tiboni, Sandra Cecconi
In this study it was evaluated if increased rounds of gonadotropin stimulation could affect in mice: i) expression levels of proteins regulating cell cycle and DNA repair in fallopian tubes and ii) meiotic spindle morphology of ovulated oocytes. To this end, adult female mice were subjected or not (Control) to 6 or 8 rounds of gonadotropin stimulation. Ovulated oocytes were incubated with anti A/B Tubulin to evaluate spindle morphology. Fallopian tubes were analyzed to detect Cyclin D1, phospho-p53/p53, phospho-AKT/AKT, phospho-GSK3B/GSK3B, SOX2, OCT3/4, phospho-B-catenin/B-catenin, phospho-CHK1, and phospho-H2A...
January 4, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
Nandini Mukherjee, Santosh Podder, Koushambi Mitra, Shamik Majumdar, Dipankar Nandi, Akhil R Chakravarty
Copper(ii) complexes [Cu(L1/L2/L3)(A)] (1-3), where H2A·HCl is a vitamin B6 Schiff base, viz. 3-hydroxy-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridin-1-ium chloride, L1 and L2 are 2-(2-pyridyl)benzimidazole based borondipyrromethene (BODIPY) ligands and L3 is 2-(2-pyridyl)benzimidazole, were prepared, characterized and their visible light-induced anti-cancer activity was studied. Complex 3, characterized by X-ray crystallography, exhibits a distorted square-pyramidal geometry for copper (τ = 0...
December 18, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
Xin Yao, Xian Cheng, Li Zhang, Huixin Yu, Jiandong Bao, Haixia Guan, Rongrong Lu
Punicalagin (PUN), a component derived from pomegranate, is well known for its anticancer activity. Our previous work revealed that PUN induces autophagic cell death in papillary thyroid carcinoma cells. We hypothesized that PUN triggers DNA damage associated with cell death because DNA damage was reported as an inducer of autophagy. Our results showed that PUN treatment caused DNA breaks as evidenced by the significant enhancement in the phosphorylation of H2A.X. However, reactive oxygen species and DNA conformational alteration, 2 common inducing factors in DNA damage, were not involved in PUN-induced DNA damage...
November 2017: Nutrition Research
Šárka Šimečková, Radek Fedr, Ján Remšík, Zuzana Kahounová, Eva Slabáková, Karel Souček
Complex analysis of cellular responses after experimental treatment is important for screening, mechanistic understanding of treatment effects, and the identification of sensitive and resistant cell phenotypes. Modern multicolor flow cytometry has demonstrated its power for such analyses. Here, we introduce a multiparametric protocol for complex analysis of cytokinetics by the simultaneous detection of seven fluorescence parameters. This analysis includes the detection of two surface markers for immunophenotyping, analysis of proliferation based on the cell cycle and the measurement of incorporated nucleoside analogue 5-ethynyl-2'-deoxyuridine (EdU) in newly synthesized DNA, analysis of DNA damage using an anti-phospho-histone H2A...
February 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Ji Hyun Cheon, Ji Yeong Kim, Byung-Mu Lee, Hyung Sik Kim, Sungpil Yoon
The present study was designed to identify conditions that could increase the sensitivity of resistant cancer cells to antimitotic drugs. We investigated whether a Janus kinase 2 (JAK2) inhibitor used in clinical trials, XL019, sensitizes antimitotic drug-resistant KBV20C cells. XL019 reduced cellular viability and increased apoptosis in vincristine-treated KBV20C cells, independently of the JAK/signal transducer and activator of transcription (STAT) pathway. Based on the ATP-binding cassette protein B1 [ABCB1, P-glycoprotein (P-gp)] inhibitory assay, we demonstrated that XL019 functions as a P-gp inhibitor in drug-resistant KBV20C cells...
December 2017: Anticancer Research
Que Wu, Zhiling Li, Yue Huang, Diting Qian, Man Chen, Wanfen Xiao, Bin Wang
In zygotes, DNA damage delays the first cleavage to enable repair. Our previous study found that 0.03 mM hydrogen peroxide (H2O2) was the minimum concentration required for induction of oxidative DNA damage in mouse zygotes and that this represented the most similar situation to the clinical phenomenon. In this study, we quantified the cleavage rates of cells in blastocysts at different developmental stages, followed by immunofluorescence to detect activation of γ-H2A histone family member X (a marker of DNA damage) in zygotes to confirm that oxidative DNA damage was induced in H2O2-treated zygotes...
2017: Oxidative Medicine and Cellular Longevity
Hyungjoo Kim, Sunhwa Oh, Myung Chan Gye, Incheol Shin
Nonylphenol polyethoxylates (NPEOs) are a major group of nonionic surfactants widely used in various detergents, cleaners, plastics, papers, and agro-chemical products. Nonylphenol (NP), which is a final degraded metabolite derived from NPEOs, has been reported as an endocrine disrupter, known to mimic or disturb reproductive hormone functions. Concern about the hazards of NP and NPEOs has generated legal restrictions and action plans worldwide. Considering the fact that NP and NPEOs are majorly used in the production of products such as detergents, shampoos, and cosmetics which frequently come into contact with the skin, we investigated the effects of NP and NPEOs on a human keratinocyte cell line (HaCaT)...
November 10, 2017: Drug and Chemical Toxicology
Jia Luo, Guocheng Pi, He Xiao, Yunfei Ye, Qing Li, Lianhua Zhao, Huan Huang, Hong Luo, Qin Zhang, Dong Wang, Ge Wang
Radiotherapy has an important role in the comprehensive treatment of breast cancer. However, the clinical outcome of adjuvant radiotherapy may be limited due to intrinsic radioresistance, it is necessary to explore efficient radiosensitization methods that improve the clinical outcome of patients undergoing radiotherapy. The present study aimed to investigate whether the novel mechanistic target of rapamycin (mTOR) inhibitor Torin2 enhances the radiosensitivity of MCF‑7 breast cancer cells. A Cell Counting Kit‑8 (CCK‑8) assay was performed to measure the effect of Torin2 on cell proliferation, while clonogenic assays were employed to determine the effect of Torin2 in combination with radiation on the proliferation of MCF‑7 cells...
January 2018: Molecular Medicine Reports
Timothy D Frouws, Philip D Barth, Timothy J Richmond
We engineered nucleosome core particles (NCPs) with two site-specific cysteine crosslinks that increase the stability of the particle. The first disulfide was introduced between the two copies of H2A via a H2A-N38C point mutation, effectively crosslinking the two H2A/H2B heterodimers together to stabilize the histone octamer against H2A/H2B dimer dissociation. The second crosslink was engineered between a R40C point mutation on the N-terminal tail of H3 and the NCP DNA ends by the introduction of a convertible nucleotide...
November 4, 2017: Journal of Molecular Biology
Romain Gioia, Simon Drouin, Manon Ouimet, Maxime Caron, Pascal St-Onge, Chantal Richer, Daniel Sinnett
Childhood acute lymphoblastic leukemia (cALL) accounts for 25% of pediatric cancers and is one of the leading causes of disease-related death in children. Although long non-coding RNAs (lncRNAs) have been implicated in cALL etiology, progression, and treatment response, little is known about their exact functional role. We had previously sequenced the whole transcriptome of 56 cALL patients and identified lncRNA transcripts specifically silenced in tumoral cells. Here we investigated the impact of restoring the expression of three of these (RP11-624C23...
October 6, 2017: Oncotarget
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