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DNA damage repair

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https://www.readbyqxmd.com/read/29150592/the-influence-of-genetic-stability-on-aspergillus-fumigatus-virulence-and-azole-resistance
#1
Thaila Fernanda Dos Reis, Lilian Pereira Silva, Patrícia Alves de Castro, Pollyne Borborema Almeida de Lima, Rafaela Andrade do Carmo, Marjorie Mendes Marini, José Franco da Silveira, Beatriz Henriques Ferreira, Fernando Rodrigues, Iran Malavazi, Gustavo H Goldman
Genetic stability is extremely important for the survival of every living organism and a very complex set of genes have evolved to cope with DNA repair upon DNA damage. Here, we investigated the Aspergillus fumigatus AtmA (Ataxia-telangiectasia mutated) and AtrA kinases and how they impact virulence and the evolution of azole resistance. We demonstrated that A. fumigatus atmA and atrA null mutants are haploid and have a discrete chromosomal polymorphism. The ΔatmA and ΔatrA strains are sensitive to several DNA damaging agents but surprisingly both strains were more resistant than the wild-type strain to paraquat, menadione, and hydrogen peroxide...
November 17, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29150048/dna-dependent-protein-kinase-modulates-the-anti-cancer-properties-of-silver-nanoparticles-in-human-cancer-cells
#2
Hui Kheng Lim, Resham Lal Gurung, M Prakash Hande
Silver nanoparticles (Ag-np) were reported to be toxic to eukaryotic cells. These potentially detrimental effects of Ag-np can be advantageous in experimental therapeutics. They are currently being employed to enhance the therapeutic efficacy of cancer drugs. In this study, we demonstrate that Ag-np treatment trigger the activation of DNA-PKcs and JNK pathway at selected doses, presumably as a physiologic response to DNA damage and repair in normal and malignant cells. Ag-np altered the telomere dynamics by disrupting the shelterin complex located at the telomeres and telomere lengths...
December 2017: Mutation Research
https://www.readbyqxmd.com/read/29149642/oxidative-stress-cell-cycle-arrest-dna-damage-and-apoptosis-in-adult-zebrafish-danio-rerio-induced-by-tris-1-3-dichloro-2-propyl-phosphate
#3
Hanyan Chen, Pingping Wang, Zhongkun Du, Guowei Wang, Shixiang Gao
Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) is an additive flame retardant of high production volume, and frequently detected in biota and environment. However, knowledge on its potential risk and toxicological mechanism still remains limited. In this study, DNA damage, transcriptomic responses and biochemical changes in the liver of zebrafish (Danio rerio) induced by TDCPP were investigated. Zebrafish was exposed to 45.81μg/L (1/100 (96h-LC50)) and 229.05μg/L (1/20 (96h-LC50)) TDCPP for 7 d. The reactive oxygen species (ROS) and GSH contents, in addition to antioxidant enzyme activities in the liver changed significantly, and the mRNA levels of genes related to oxidative stress were alerted in a dose-dependent and/or sex-dependent manner after exposure to TDCPP...
November 10, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29149600/repair-of-uv-induced-dna-damage-independent-of-nucleotide-excision-repair-is-masked-by-mutyh
#4
Abdelghani Mazouzi, Federica Battistini, Sarah C Moser, Joana Ferreira da Silva, Marc Wiedner, Michel Owusu, Charles-Hugues Lardeau, Anna Ringler, Beatrix Weil, Jürgen Neesen, Modesto Orozco, Stefan Kubicek, Joanna I Loizou
DNA lesions caused by UV damage are thought to be repaired solely by the nucleotide excision repair (NER) pathway in human cells. Patients carrying mutations within genes functioning in this pathway display a range of pathologies, including an increased susceptibility to cancer, premature aging, and neurological defects. There are currently no curative therapies available. Here we performed a high-throughput chemical screen for agents that could alleviate the cellular sensitivity of NER-deficient cells to UV-induced DNA damage...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149412/the-translationally-controlled-tumor-protein-and-the-cellular-response-to-ionizing-radiation-induced-dna-damage
#5
Jie Zhang, Grace Shim, Sonia M de Toledo, Edouard I Azzam
The absorption of ionizing radiation by living cells can directly disrupt atomic structures, producing chemical and biological changes. It can also act indirectly through radiolysis of water, thereby generating reactive chemical species that may damage nucleic acids, proteins, and lipids. Together, the direct and indirect effects of radiation initiate a series of biochemical and molecular signaling events that may repair the damage or culminate in permanent physiological changes or cell death. In efforts to gain insight into the mechanisms underlying these effects, we observed a prominent upregulation of the Translationally Controlled Tumor Protein (TCTP) in low dose/low dose rate (137)Cs γ-irradiated cells that was associated with adaptive responses that reduced chromosomal damage to a level lower than what occurs spontaneously...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149404/the-translational-controlled-tumour-protein-tctp-biological-functions-and-regulation
#6
Ulrich-Axel Bommer
The Translational Controlled Tumour Protein TCTP (gene symbol TPT1, also called P21, P23, Q23, fortilin or histamine-releasing factor, HRF) is a highly conserved protein present in essentially all eukaryotic organisms and involved in many fundamental cell biological and disease processes. It was first discovered about 35 years ago, and it took an extended period of time for its multiple functions to be revealed, and even today we do not yet fully understand all the details. Having witnessed most of this history, in this chapter, I give a brief overview and review the current knowledge on the structure, biological functions, disease involvements and cellular regulation of this protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149203/alc1-chd1l-a-chromatin-remodeling-enzyme-is-required-for-efficient-base-excision-repair
#7
Masataka Tsuda, Kosai Cho, Masato Ooka, Naoto Shimizu, Reiko Watanabe, Akira Yasui, Yuka Nakazawa, Tomoo Ogi, Hiroshi Harada, Keli Agama, Jun Nakamura, Ryuta Asada, Haruna Fujiike, Tetsushi Sakuma, Takashi Yamamoto, Junko Murai, Masahiro Hiraoka, Kaoru Koike, Yves Pommier, Shunichi Takeda, Kouji Hirota
ALC1/CHD1L is a member of the SNF2 superfamily of ATPases carrying a macrodomain that binds poly(ADP-ribose). Poly(ADP-ribose) polymerase (PARP) 1 and 2 synthesize poly(ADP-ribose) at DNA-strand cleavage sites, promoting base excision repair (BER). Although depletion of ALC1 causes increased sensitivity to various DNA-damaging agents (H2O2, UV, and phleomycin), the role played by ALC1 in BER has not yet been established. To explore this role, as well as the role of ALC1's ATPase activity in BER, we disrupted the ALC1 gene and inserted the ATPase-dead (E165Q) mutation into the ALC1 gene in chicken DT40 cells, which do not express PARP2...
2017: PloS One
https://www.readbyqxmd.com/read/29149101/how-does-p53-induce-apoptosis-and-how-does-this-relate-to-p53-mediated-tumour-suppression
#8
REVIEW
Brandon J Aubrey, Gemma L Kelly, Ana Janic, Marco J Herold, Andreas Strasser
The tumour suppressor gene TP53 is mutated in ~50% of human cancers. In addition to its function in tumour suppression, p53 also plays a major role in the response of malignant as well as nontransformed cells to many anticancer therapeutics, particularly those that cause DNA damage. P53 forms a homotetrameric transcription factor that is reported to directly regulate ~500 target genes, thereby controlling a broad range of cellular processes, including cell cycle arrest, cell senescence, DNA repair, metabolic adaptation and cell death...
November 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29149093/evolutionarily-distant-streptophyta-respond-differently-to-genotoxic-stress
#9
Radka Vágnerová, Alena Lukešová, Martin Lukeš, Petra Rožnovská, Marcela Holá, Jana Fulnečková, Jiří Fajkus, Karel J Angelis
Research in algae usually focuses on the description and characterization of morpho-and phenotype as a result of adaptation to a particular habitat and its conditions. To better understand the evolution of lineages we characterized responses of filamentous streptophyte green algae of the genera Klebsormidium and Zygnema, and of a land plant-the moss Physcomitrellapatens-to genotoxic stress that might be relevant to their environment. We studied the induction and repair of DNA double strand breaks (DSBs) elicited by the radiomimetic drug bleomycin, DNA single strand breaks (SSB) as consequence of base modification by the alkylation agent methyl methanesulfonate (MMS) and of ultra violet (UV)-induced photo-dimers, because the mode of action of these three genotoxic agents is well understood...
November 17, 2017: Genes
https://www.readbyqxmd.com/read/29147457/oxidative-stress-delays-prometaphase-metaphase-of-the-first-cleavage-in-mouse-zygotes-via-the-mad2l1-mediated-spindle-assembly-checkpoint
#10
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
https://www.readbyqxmd.com/read/29145667/planarians-customize-their-stem-cell-responses-following-genotoxic-stress-as-a-function-of-exposure-time-and-regenerative-state
#11
An-Sofie Stevens, Annelies Wouters, Jan-Pieter Ploem, Nicky Pirotte, Andromeda Van Roten, Maxime Willems, Niels Hellings, Carmen Franken, Gudrun Koppen, Tom Artois, Michelle Plusquin, Karen Smeets
Aiming to in vivo characterise the responses of pluripotent stem cells and regenerative tissues to carcinogenic stress, we employed the highly regenerative organism Schmidtea mediterranea. Its broad regenerative capacities are attributable to a large pool of pluripotent stem cells, which are considered key players in the lower vulnerability towards chemically-induced carcinogenesis observed in regenerative organisms. S. mediterranea is, therefore, an ideal model to study pluripotent stem cell responses with stem cells residing in their natural environment...
November 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29144457/a-ubiquitin-dependent-signalling-axis-specific-for-alkbh-mediated-dna-dealkylation-repair
#12
Joshua R Brickner, Jennifer M Soll, Patrick M Lombardi, Cathrine B Vågbø, Miranda C Mudge, Clement Oyeniran, Renana Rabe, Jessica Jackson, Meagan E Sullender, Elyse Blazosky, Andrea K Byrum, Yu Zhao, Mark A Corbett, Jozef Gécz, Michael Field, Alessandro Vindigni, Geir Slupphaug, Cynthia Wolberger, Nima Mosammaparast
DNA repair is essential to prevent the cytotoxic or mutagenic effects of various types of DNA lesions, which are sensed by distinct pathways to recruit repair factors specific to the damage type. Although biochemical mechanisms for repairing several forms of genomic insults are well understood, the upstream signalling pathways that trigger repair are established for only certain types of damage, such as double-stranded breaks and interstrand crosslinks. Understanding the upstream signalling events that mediate recognition and repair of DNA alkylation damage is particularly important, since alkylation chemotherapy is one of the most widely used systemic modalities for cancer treatment and because environmental chemicals may trigger DNA alkylation...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29143133/association-of-dna-repair-genes-polymorphisms-and-mutations-with-increased-risk-of-head-and-neck-cancer-a-review
#13
REVIEW
Agata Dylawerska, Wojciech Barczak, Anna Wegner, Wojciech Golusinski, Wiktoria Maria Suchorska
DNA repair mechanisms allow maintain genomic stability and proper functioning within the cells. Any aberrations may cause an increased risk of many diseases such as cancer. The most crucial risk factors for head and neck squamous cell carcinoma are behavioral factors, predominantly chronic exposure to tobacco, alcohol addiction, and infection with human papillomavirus or Epstein-Barr virus. These agents can induce DNA damage; therefore, cells must activate appropriate mechanisms in order to function correctly...
November 15, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29142067/jq1-induces-dna-damage-and-apoptosis-and-inhibits-tumor-growth-in-a-patient-derived-xenograft-model-of-cholangiocarcinoma
#14
Patrick L Garcia, Aubrey L Miller, Tracy L Gamblin, Leona N Council, John D Christein, J Pablo Arnoletti, Marty J Heslin, Sushanth Reddy, Joseph H Richardson, Xiangqin Cui, Robert C A M van Waardenburg, James E Bradner, Eddy S Yang, Karina J Yoon
Cholangiocarcinoma (CCA) is a fatal disease with a five-year survival of <30%. For a majority of patients chemotherapy is the only therapeutic option, and virtually all patients relapse. Gemcitabine is the frontline agent for treatment of CCA. Patients treated with gemcitabine monotherapy survive ~8 months. Combining this agent with cisplatin increases survival by ~3 months, but neither regimen produces durable remissions. The molecular etiology of this disease is poorly understood. To facilitate molecular characterization and development of effective therapies for CCA, we established a panel of patient-derived xenograft (PDX) models of CCA...
November 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29141977/vitamins-associated-with-brain-aging-mild-cognitive-impairment-and-alzheimer-disease-biomarkers-epidemiological-and-experimental-evidence-plausible-mechanisms-and-knowledge-gaps
#15
REVIEW
Michael Fenech
The key to preventing brain aging, mild cognitive impairment (MCI), and Alzheimer disease (AD) via vitamin intake is first to understand molecular mechanisms, then to deduce relevant biomarkers, and subsequently to test the level of evidence for the impact of vitamins in the relevant pathways and their modulation of dementia risk. This narrative review infers information on mechanisms from gene and metabolic defects associated with MCI and AD, and assesses the role of vitamins using recent results from animal and human studies...
November 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/29141549/a-high-throughput-quantitative-expression-analysis-of-cancer-related-genes-in-human-hepg2-cells-in-response-to-limonene-a-potential-anticancer-agent
#16
Rand R Hafidh, Saba Z Hussein, Mohammed Q MalAllah, Ahmed S Abdulamir, Fatimah Abu Bakar
BACKGROUND: Citrus bioactive compounds, as active anticancer agent, have been under focus by several studies worldwide. However, the underlying genes responsible for the anticancer potential have not been sufficiently highlighted. OBJECTIVES: The current study investigated the gene expression profile of hepatocellular carcinoma, HepG2, cells after treatment with Limonene. METHODS: The concentration that killed 50% of HepG2 cells was used to elucidate the genetic mechanisms of limonene anticancer activity...
November 14, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29140459/rbm45-competes-with-hdac1-for-binding-to-fus-in-response-to-dna-damage
#17
Juanjuan Gong, Min Huang, Fengli Wang, Xiaolu Ma, Hongmei Liu, Yingfeng Tu, Lingyu Xing, Xuefei Zhu, Hui Zheng, Junjie Fang, Xiaoling Li, Qiaochu Wang, Jiuqiang Wang, Zhongshuai Sun, Xi Wang, Yun Wang, Caixia Guo, Tie-Shan Tang
DNA damage response (DDR) is essential for genome stability and human health. Recently, several RNA binding proteins (RBPs), including fused-in-sarcoma (FUS), have been found unexpectedly to modulate this process. The role of FUS in DDR is closely linked to the pathogenesis of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Given that RBM45 is also an ALS-associated RBP, we wondered whether RBM45 plays any function during this process...
November 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29138572/current-status-of-poly-adp-ribose-polymerase-inhibitors-and-future-directions
#18
REVIEW
Akihiro Ohmoto, Shinichi Yachida
Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA-mutant ovarian cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29137397/dna-mismatch-repair-protein-mlh1-is-required-for-tetravalent-chromium-intermediate-induced-dna-damage
#19
Timothy P Wakeman, Aimin Yang, Naresh S Dalal, Rebecca J Boohaker, Qinghua Zeng, Qiang Ding, Bo Xu
Hexavalent chromium (Cr[VI]) is associated with occupational lung cancer and poses a significant public health concern. When exposed to Cr[VI], cells rapidly internalize this compound and metabolize it to Cr[III]. Byproducts of Cr[VI] metabolism include unstable Cr[V] and Cr[IV] intermediates that are believed to be directly responsible for the genotoxicity and carcinogenicity caused by Cr[VI] exposure; however, the carcinogenic potential of the Cr intermediates and the mechanisms of Cr-induced carcinogenesis remain to be further defined...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137223/hormone-induced-dna-damage-response-and-repair-mediated-by-cyclin-d1-in-breast-and-prostate-cancer
#20
REVIEW
Gabriele Di Sante, Agnese Di Rocco, Claudia Pupo, Mathew C Casimiro, Richard G Pestell
Cell cycle control proteins govern events that leads to the production of two identical daughter cells. Distinct sequential temporal phases, Gap 1 (G1), Gap 0 (G0), Synthesis (S), Gap 2 (G2) and Mitosis (M) are negotiated through a series of check points during which the favorability of the local cellular environment is assessed, prior to replicating DNA [1]. Cyclin D1 has been characterized as a key regulatory subunit of the holoenzyme that promotes the G1/S-phase transition through phosphorylating the pRB protein...
October 10, 2017: Oncotarget
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