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Dna repair and autophagy

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https://www.readbyqxmd.com/read/28611823/genetic-variability-as-a-regulator-of-tlr4-and-nod-signaling-in-response-to-bacterial-driven-dna-damage-response-ddr-and-inflammation-focus-on-the-gastrointestinal-gi-tract
#1
REVIEW
Evagelia Spanou, Polyxeni Kalisperati, Ioannis S Pateras, Alexandros Papalampros, Alexandra Barbouti, Athanasios G Tzioufas, Athanassios Kotsinas, Stavros Sougioultzis
The fundamental role of human Toll-like receptors (TLRs) and NOD-like receptors (NLRs), the two most studied pathogen recognition receptors (PRRs), is the protection against pathogens and excessive tissue injury. Recent evidence supports the association between TLR/NLR gene mutations and susceptibility to inflammatory, autoimmune, and malignant diseases. PRRs also interfere with several cellular processes, such as cell growth, apoptosis, cell proliferation, differentiation, autophagy, angiogenesis, cell motility and migration, and DNA repair mechanisms...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28574824/the-dual-role-and-therapeutic-potential-of-high-mobility-group-box-1-in-cancer
#2
REVIEW
Si-Jia He, Jin Cheng, Xiao Feng, Yang Yu, Ling Tian, Qian Huang
High-mobility group box 1 (HMGB1) is an abundant protein in most eukaryocytes. It can bind to several receptors such as advanced glycation end products (RAGE) and Toll-like receptors (TLRs), in direct or indirect way. The biological effects of HMGB1 depend on its expression and subcellular location. Inside the nucleus, HMGB1 is engaged in many DNA events such as DNA repair, transcription, telomere maintenance, and genome stability. While outside the nucleus, it possesses more complicated functions, including regulating cell proliferation, autophagy, inflammation and immunity...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28558867/apigenin-s-anticancer-properties-and-molecular-mechanisms-of-action-recent-advances-and-future-prospectives
#3
Jumah Masoud Mohammad Salmani, Xiao-Ping Zhang, Joe Antony Jacob, Bao-An Chen
Cancer is a major health concern and leading burden on economy worldwide. An increasing effort is devoted to isolation and development of plant-derived dietary components as effective chemo-preventive products. Phytochemical compounds from natural resources such as fruits and vegetables are responsible for decreasing the risk of certain cancers among the consuming populations. Apigenin, a flavonoid phytochemical found in many kinds of fruits and vegetables, has been shown to exert significant biological effects, such as anti-oxidant, anti-inflammatory and most particularly anti-neoplastic properties...
May 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28543935/neurodegeneration-in-ataxia-telangiectasia-multiple-roles-of-atm-kinase-in-cellular-homeostasis
#4
REVIEW
Kay Rui Choy, Dianne J Watters
Ataxia-Telangiectasia (A-T) is characterized by neuronal degeneration, cancer, diabetes, immune deficiency and increased sensitivity to ionizing radiation. A-T is attributed to the deficiency of the protein kinase coded by the ATM (Ataxia-Telangiectasia Mutated) gene. ATM is a sensor of DNA Double Strand Breaks and signals to cell cycle checkpoints and the DNA repair machinery. ATM phosphorylates numerous substrates and activates many cell-signalling pathways. There has been considerable debate about whether a defective DNA damage response is causative of the neurological aspects of the disease...
May 22, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28526407/sirtuin-inhibition-leads-to-autophagy-and-apoptosis-in-porcine-preimplantation-blastocysts
#5
Min Gyeong Kim, Duk Hyoun Kim, Hye Ran Lee, Jun Sung Lee, Su Jin Jin, Hoon Taek Lee
Sirtuins are nicotinamide adenine dinucleotide dependent class III histone deacetylase proteins that play a crucial role in several cellular processes, including DNA repair, apoptosis, and lifespan. Previous studies have shown that sirtuin inhibition leads to embryonic developmental arrest and oxidative stress in porcine and murine. However, sirtuin-mediated mechanisms have not been examined in porcine preimplantation blastocysts. We therefore investigated the relationship between sirtuins and autophagy. Embryos were cultured with 100 μM sirtinol (SIRT1/2 inhibitor) in NCSU-23 media after in vitro fertilization...
May 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28522553/glioblastoma-derived-cells-in-vitro-unveil-the-spectrum-of-drug-resistance-capabilty-comparative-study-of-tumour-chemosensitivity-in-different-culture-systems
#6
Monika Witusik-Perkowska, Magdalena Zakrzewska, Beata Sikorska, Wielislaw Papierz, Dariusz J Jaskolski, Janusz Szemraj, Pawel P Liberski
Resistance to cancer drugs is a complex phenomenon which could be influenced by in vitro conditions. However, tumour-derived cell cultures are routinely used for studies related to mechanisms of drug responsiveness or the search for new therapeutic approaches. The purpose of our work was to identify the potential differences in drug resistance and response to treatment of glioblastoma with the use of three in vitro models: traditional adherent culture, serum-free spheroid culture and novel adherent serum-free culture...
May 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28512061/genetic-variants-in-autophagy-associated-genes-are-associated-with-dna-damage-levels-in-chinese-population
#7
Zhihua Li, Junyi Xin, Weihong Chen, Jia Liu, Meng Zhu, Congwen Zhao, Jing Yuan, Guangfu Jin, Hongxia Ma, Jiangbo Du, Zhibin Hu, Tangchun Wu, Hongbing Shen, Juncheng Dai, Hao Yu
Autophagy associated genes (ATGs) played an important role in the repair process of DNA damage and decreased autophagy may weaken the repair process and aggravate DNA damage. Based on this, we hypothesized that DNA damage levels might be modified by genetic variants in autophagy associated genes. In order to validate our hypothesis, 307 subjects were recruited from three different cities (Zhuhai, Wuhan and Tianjin) in China. Demographic data, individual 24-h PM2.5 exposure and peripheral blood DNA damage levels were also detected...
May 13, 2017: Gene
https://www.readbyqxmd.com/read/28509385/molecular-events-leading-to-death-of-leishmania-donovani-under-spermidine-starvation-after-hypericin-treatment
#8
Shalini Singh, Ekta Kumari, Ruchika Bhardwaj, Ritesh Kumar, Vikash Kumar Dubey
We have previously reported that the hypericin treatment caused spermidine starvation and death of Leishmania parasite. Here, we report different molecular events under spermidine starvation and potential role of spermidine in processes other than redox homeostasis of the parasite. We have analyzed changes in expression of several genes by using quantitative gene expression analysis. Further, these changes at molecular level were also confirmed by using biochemical and cellular studies. Altered expression of several genes involved in redox metabolism, hypusine modification of eIF5A, DNA repair pathway and autophagy was observed...
May 16, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28465145/energy-sensing-pathways-bridging-type-2-diabetes-and-colorectal-cancer
#9
REVIEW
Juhong Yang, Reiko Nishihara, Xuehong Zhang, Shuji Ogino, Zhi Rong Qian
The recently rapid increase of obesity and type 2 diabetes mellitus has caused great burden to our society. A positive association between type 2 diabetes and risk of colorectal cancer has been reported by increasing epidemiological studies. The molecular mechanism of this connection remains elusive. However, type 2 diabetes may result in abnormal carbohydrate and lipid metabolism, high levels of circulating insulin, insulin growth factor-1, and adipocytokines, as well as chronic inflammation. All these factors could lead to the alteration of energy sensing pathways such as the AMP activated kinase (PRKA), mechanistic (mammalian) target of rapamycin (mTOR), SIRT1, and autophagy signaling pathways...
April 13, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28453550/selective-mitochondrial-dna-degradation-following-double-strand-breaks
#10
Amandine Moretton, Frédéric Morel, Bertil Macao, Philippe Lachaume, Layal Ishak, Mathilde Lefebvre, Isabelle Garreau-Balandier, Patrick Vernet, Maria Falkenberg, Géraldine Farge
Mitochondrial DNA (mtDNA) can undergo double-strand breaks (DSBs), caused by defective replication, or by various endogenous or exogenous sources, such as reactive oxygen species, chemotherapeutic agents or ionizing radiations. MtDNA encodes for proteins involved in ATP production, and maintenance of genome integrity following DSBs is thus of crucial importance. However, the mechanisms involved in mtDNA maintenance after DSBs remain unknown. In this study, we investigated the consequences of the production of mtDNA DSBs using a human inducible cell system expressing the restriction enzyme PstI targeted to mitochondria...
2017: PloS One
https://www.readbyqxmd.com/read/28451587/the-interplay-of-cofactor-interactions-and-post-translational-modifications-in-the-regulation-of-the-aaa-atpase-p97
#11
REVIEW
Petra Hänzelmann, Hermann Schindelin
The hexameric type II AAA ATPase (ATPase associated with various activities) p97 (also referred to as VCP, Cdc48, and Ter94) is critically involved in a variety of cellular activities including pathways such as DNA replication and repair which both involve chromatin remodeling, and is a key player in various protein quality control pathways mediated by the ubiquitin proteasome system as well as autophagy. Correspondingly, p97 has been linked to various pathophysiological states including cancer, neurodegeneration, and premature aging...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28427237/oxidative-dna-double-strand-breaks-and-autophagy-in-the-antitumor-effect-of-sterically-hindered-platinum-ii-complexes-in-nsclcs
#12
Feihong Chen, Xinyi Wang, Xiufeng Jin, Jian Zhao, Shaohua Gou
A series of novel platinum(II) complexes with (1R,2R)-N1,N2-diisobutyl-1,2-diaminocyclohexane as a carrier ligand, while N1,N2-diisobutyl moiety serving as steric hindrance were designed, synthesized and characterized. The in vitro biological assays demonstrated that complex 3 had increased cytotoxicity against lung cancer cells, especially non-small-cell lung cancer (NSCLC) compared to its mono-substituted complex 3a, indicating that the sterically hindered alkyl moieties have significant influences on its antitumor property...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423511/atm-kinase-sustains-breast-cancer-stem-like-cells-by-promoting-atg4c-expression-and-autophagy
#13
Martina Antonelli, Flavie Strappazzon, Ivan Arisi, Rossella Brandi, Mara D'Onofrio, Manolo Sambucci, Gwenola Manic, Ilio Vitale, Daniela Barilà, Venturina Stagni
The efficacy of Ataxia-Telangiectasia Mutated (ATM) kinase signalling inhibition in cancer therapy is tempered by the identification of new emerging functions of ATM, which suggests that the role of this protein in cancer progression is complex. We recently demonstrated that this tumor suppressor gene could act as tumor promoting factor in HER2 (Human Epidermal Growth Factor Receptor 2) positive breast cancer. Herein we put in evidence that ATM expression sustains the proportion of cells with a stem-like phenotype, measured as the capability to form mammospheres, independently of HER2 expression levels...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28373404/precancer-atlas-to-drive-precision-prevention-trials
#14
Avrum Spira, Matthew B Yurgelun, Ludmil Alexandrov, Anjana Rao, Rafael Bejar, Kornelia Polyak, Marios Giannakis, Ali Shilatifard, Olivera J Finn, Madhav Dhodapkar, Neil E Kay, Esteban Braggio, Eduardo Vilar, Sarah A Mazzilli, Timothy R Rebbeck, Judy E Garber, Victor E Velculescu, Mary L Disis, Douglas C Wallace, Scott M Lippman
Cancer development is a complex process driven by inherited and acquired molecular and cellular alterations. Prevention is the holy grail of cancer elimination, but making this a reality will take a fundamental rethinking and deep understanding of premalignant biology. In this Perspective, we propose a national concerted effort to create a Precancer Atlas (PCA), integrating multi-omics and immunity - basic tenets of the neoplastic process. The biology of neoplasia caused by germline mutations has led to paradigm-changing precision prevention efforts, including: tumor testing for mismatch repair (MMR) deficiency in Lynch syndrome establishing a new paradigm, combinatorial chemoprevention efficacy in familial adenomatous polyposis (FAP), signal of benefit from imaging-based early detection research in high-germline risk for pancreatic neoplasia, elucidating early ontogeny in BRCA1-mutation carriers leading to an international breast cancer prevention trial, and insights into the intricate germline-somatic-immunity interaction landscape...
April 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28345663/nuclear-localization-of-beclin-1-promotes-radiation-induced-dna-damage-repair-independent-of-autophagy
#15
Fei Xu, Yixuan Fang, Lili Yan, Lan Xu, Suping Zhang, Yan Cao, Li Xu, Xiaoying Zhang, Jialing Xie, Gaoyue Jiang, Chaorong Ge, Ni An, Daohong Zhou, Na Yuan, Jianrong Wang
Beclin 1 is a well-established core mammalian autophagy protein that is embryonically indispensable and has been presumed to suppress oncogenesis via an autophagy-mediated mechanism. Here, we show that Beclin 1 is a prenatal primary cytoplasmic protein but rapidly relocated into the nucleus during postnatal development in mice. Surprisingly, deletion of beclin1 in in vitro human cells did not block an autophagy response, but attenuated the expression of several DNA double-strand break (DSB) repair proteins and formation of repair complexes, and reduced an ability to repair DNA in the cells exposed to ionizing radiation (IR)...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28342984/hdac4-and-hdac6-sustain-dna-double-strand-break-repair-and-stem-like-phenotype-by-promoting-radioresistance-in-glioblastoma-cells
#16
Francesco Marampon, Francesca Megiorni, Simona Camero, Clara Crescioli, Heather P McDowell, Roberta Sferra, Antonella Vetuschi, Simona Pompili, Luca Ventura, Francesca De Felice, Vincenzo Tombolini, Carlo Dominici, Roberto Maggio, Claudio Festuccia, Giovanni Luca Gravina
The role of histone deacetylase (HDAC) 4 and 6 in glioblastoma (GBM) radioresistance was investigated. We found that tumor samples from 31 GBM patients, who underwent temozolomide and radiotherapy combined treatment, showed HDAC4 and HDAC6 expression in 93.5% and 96.7% of cases, respectively. Retrospective clinical data analysis demonstrated that high-intensity HDAC4 and/or HDAC6 immunostaining was predictive of poor clinical outcome. In vitro experiments revealed that short hairpin RNA-mediated silencing of HDAC4 or HDAC6 radiosensitized U87MG and U251MG GBM cell lines by promoting DNA double-strand break (DSBs) accumulation and by affecting DSBs repair molecular machinery...
March 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28327001/autophagy-promotes-the-repair-of-radiation-induced-dna-damage-in-bone-marrow-hematopoietic-cells-via-enhanced-stat3-signaling
#17
Fei Xu, Xin Li, Lili Yan, Na Yuan, Yixuan Fang, Yan Cao, Li Xu, Xiaoying Zhang, Lan Xu, Chaorong Ge, Ni An, Gaoyue Jiang, Jialing Xie, Han Zhang, Jiayi Jiang, Xiaotian Li, Lei Yao, Suping Zhang, Daohong Zhou, Jianrong Wang
Autophagy protects hematopoietic cells from radiation damage in part by promoting DNA damage repair. However, the molecular mechanisms by which autophagy regulates DNA damage repair remain largely elusive. Here, we report that this radioprotective effect of autophagy depends on STAT3 signaling in murine bone marrow mononuclear cells (BM-MNCs). Specifically, we found that STAT3 activation and nuclear translocation in BM-MNCs were increased by activation of autophagy with an mTOR inhibitor and decreased by knockout of the autophagy gene Atg7...
March 2017: Radiation Research
https://www.readbyqxmd.com/read/28292950/papers-of-note-in-nature543-7644
#18
Annalisa M VanHook
This week's articles highlight the role of autophagy in maintaining stem cells and a new player in the repair of double-strand DNA breaks.
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28288132/census-and-evaluation-of-p53-target-genes
#19
REVIEW
M Fischer
The tumor suppressor p53 functions primarily as a transcription factor. Mutation of the TP53 gene alters its response pathway, and is central to the development of many cancers. The discovery of a large number of p53 target genes, which confer p53's tumor suppressor function, has led to increasingly complex models of p53 function. Recent meta-analysis approaches, however, are simplifying our understanding of how p53 functions as a transcription factor. In the survey presented here, a total set of 3661 direct p53 target genes is identified that comprise 3509 potential targets from 13 high-throughput studies, and 346 target genes from individual gene analyses...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28283188/targeted-cytoplasmic-irradiation-and-autophagy
#20
Jinhua Wu, Bo Zhang, Yen-Ruh Wuu, Mercy M Davidson, Tom K Hei
The effect of ionizing irradiation on cytoplasmic organelles is often underestimated because the general dogma considers direct DNA damage in the nuclei to be the primary cause of radiation induced toxicity. Using a precision microbeam irradiator, we examined the changes in mitochondrial dynamics and functions triggered by targeted cytoplasmic irradiation with α-particles. Mitochondrial dysfunction induced by targeted cytoplasmic irradiation led to activation of autophagy, which degraded dysfunctional mitochondria in order to maintain cellular energy homeostasis...
March 1, 2017: Mutation Research
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