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Dna repair and autophagy

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https://www.readbyqxmd.com/read/27917193/dna-damage-response-and-autophagy-a-meaningful-partnership
#1
REVIEW
Aristides G Eliopoulos, Sophia Havaki, Vassilis G Gorgoulis
Autophagy and the DNA damage response (DDR) are biological processes essential for cellular and organismal homeostasis. Herein, we summarize and discuss emerging evidence linking DDR to autophagy. We highlight published data suggesting that autophagy is activated by DNA damage and is required for several functional outcomes of DDR signaling, including repair of DNA lesions, senescence, cell death, and cytokine secretion. Uncovering the mechanisms by which autophagy and DDR are intertwined provides novel insight into the pathobiology of conditions associated with accumulation of DNA damage, including cancer and aging, and novel concepts for the development of improved therapeutic strategies against these pathologies...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27908782/adaptive-responses-of-neuronal-mitochondria-to-bioenergetic-challenges-roles-in-neuroplasticity-and-disease-resistance
#2
REVIEW
Sophia M Raefsky, Mark P Mattson
An important concept in neurobiology is "neurons that fire together, wire together" which means that the formation and maintenance of synapses is promoted by activation of those synapses. Very similar to the effects of the stress of exercise on muscle cells, emerging findings suggest that neurons respond to activity by activating signaling pathways (e.g., Ca(2+), CREB, PGC-1α, NF-κB) that stimulate mitochondrial biogenesis and cellular stress resistance. These pathways are also activated by aerobic exercise and food deprivation, two bioenergetic challenges of fundamental importance in the evolution of the brains of all mammals, including humans...
November 29, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27899501/unraveling-fungal-radiation-resistance-regulatory-networks-through-the-genome-wide-transcriptome-and-genetic-analyses-of-cryptococcus-neoformans
#3
Kwang-Woo Jung, Dong-Hoon Yang, Min-Kyu Kim, Ho Seong Seo, Sangyong Lim, Yong-Sun Bahn
The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation...
November 29, 2016: MBio
https://www.readbyqxmd.com/read/27857976/autophagy-regulates-dna-repair-by-modulating-histone-ubiquitination
#4
Yanan Wang, Wei-Guo Zhu, Ying Zhao
Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. Here, we report that the autophagy receptor and substrate p62/SQSTM1 inhibits DNA double-strand break -induced histone and chromatin ubiquitination, which has a critical role in attracting key repair factors to the break sites.
2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27810402/impact-of-intermittent-fasting-on-health-and-disease-processes
#5
REVIEW
Mark P Mattson, Valter D Longo, Michelle Harvie
Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state...
October 31, 2016: Ageing Research Reviews
https://www.readbyqxmd.com/read/27807740/reduced-risk-of-apoptosis-mechanisms-of-stress-responses
#6
Irina Milisav, Borut Poljšak, Samo Ribarič
Apoptosis signaling pathways are integrated into a wider network of interconnected apoptotic and anti-apoptotic pathways that regulate a broad range of cell responses from cell death to growth, development and stress responses. An important trigger for anti- or pro-apoptotic cell responses are different forms of stress including hypoxia, energy deprivation, DNA damage or inflammation. Stress duration and intensity determine whether the cell's response will be improved cell survival, due to stress adaptation, or cell death by apoptosis, necrosis or autophagy...
November 2, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27805285/survivin-inhibitor-ym155-induces-mitochondrial-dysfunction-autophagy-dna-damage-and-apoptosis-in-bcl-xl-silenced-glioma-cell-lines
#7
Esther P Jane, Daniel R Premkumar, Philip A Sutera, Jonathon M Cavaleri, Ian F Pollack
Because the anti-apoptotic protein Bcl-xL is overexpressed in glioma, one might expect that inhibiting or silencing this gene would promote tumor cell killing. However, our studies have shown that this approach has limited independent activity, but may tip the balance in favor of apoptosis induction in response to other therapeutic interventions. To address this issue, we performed a pharmacological screen using a panel of signaling inhibitors and chemotherapeutic agents in Bcl-xL silenced cells. Although limited apoptosis induction was observed with a series of inhibitors for receptor tyrosine kinases, PKC inhibitors, Src family members, JAK/STAT, histone deacetylase, the PI3K/Akt/mTOR pathway, MAP kinase, CDK, heat shock proteins, proteasomal processing, and various conventional chemotherapeutic agents, we observed a dramatic potentiation of apoptosis in Bcl-xL silenced cells with the survivin inhibitor, YM155...
November 2, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27791533/autophagy-substrate-sqstm1-p62-regulates-chromatin-ubiquitination-during-the-dna-damage-response
#8
Yanan Wang, Wei-Guo Zhu, Ying Zhao
The importance of autophagy in the DNA damage repair process is clear; however, the detailed molecular mechanism is still largely unknown. Here we found that DNA damage-induced histone H2A ubiquitination is suppressed in autophagy-deficient cells in a SQSTM1/p62 dependent manner. SQSTM1 binds and inhibits E3 ligase RNF168s activity, which is essential for H2A ubiquitination. As a result, several important factors for DNA repair cannot be recruited to the sites of DNA double-strand breaks (DSBs) in autophagy-deficient cells, leading to diminished DNA repair and increased sensitivity of cells to radiation...
October 28, 2016: Autophagy
https://www.readbyqxmd.com/read/27788957/targeting-phosphatidylinositol-4-kinase-iii%C3%AE-for-radiosensitization-a-potential-model-of-drug-repositioning-using-an-anti-hepatitis-c-viral-agent
#9
Jeanny Kwon, Dan Hyo Kim, Ji Min Park, Young Hee Park, Yeo Hyun Hwang, Hong-Gyun Wu, Kyung Hwan Shin, In Ah Kim
PURPOSE: To investigate which isotype of phosphatidylinositol 4-kinase (PI4K) may affect radiosensitivity and examine whether anti-hepatitis C viral (HCV) agents, some of which have been shown to inhibit PI4K IIIα activity, could be repositioned as a radiosensitizer in human cancer cells. METHODS AND MATERIALS: U251, BT474, and HepG2 cell lines and normal human astrocyte were used. Ribonucleic acid interference, clonogenic assays, Western blotting, immunofluorescence, annexin V assay, lysotracker staining, and β-galactosidase assay were performed...
November 15, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27773819/fancd2-protects-against-bone-marrow-injury-from-ferroptosis
#10
Xinxin Song, Yangchun Xie, Rui Kang, Wen Hou, Xiaofang Sun, Michael W Epperly, Joel S Greenberger, Daolin Tang
Bone marrow injury remains a serious concern in traditional cancer treatment. Ferroptosis is an iron- and oxidative-dependent form of regulated cell death that has become part of an emerging strategy for chemotherapy. However, the key regulator of ferroptosis in bone marrow injury remains unknown. Here, we show that Fanconi anemia complementation group D2 (FANCD2), a nuclear protein involved in DNA damage repair, protects against ferroptosis-mediated injury in bone marrow stromal cells (BMSCs). The classical ferroptosis inducer erastin remarkably increased the levels of monoubiquitinated FANCD2, which in turn limited DNA damage in BMSCs...
October 20, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27757073/a-decade-of-boon-or-burden-what-has-the-chip-ever-done-for-cellular-protein-quality-control-mechanism-implicated-in-neurodegeneration-and-aging
#11
Vibhuti Joshi, Ayeman Amanullah, Arun Upadhyay, Ribhav Mishra, Amit Kumar, Amit Mishra
Cells regularly synthesize new proteins to replace old and abnormal proteins for normal cellular functions. Two significant protein quality control pathways inside the cellular milieu are ubiquitin proteasome system (UPS) and autophagy. Autophagy is known for bulk clearance of cytoplasmic aggregated proteins, whereas the specificity of protein degradation by UPS comes from E3 ubiquitin ligases. Few E3 ubiquitin ligases, like C-terminus of Hsc70-interacting protein (CHIP) not only take part in protein quality control pathways, but also plays a key regulatory role in other cellular processes like signaling, development, DNA damage repair, immunity and aging...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27748893/crosstalk-between-autophagy-and-intracellular-radiation-response-review
#12
Lelin Hu, Hao Wang, Li Huang, Yong Zhao, Junjie Wang
Autophagy induced by radiation is critical to cell fate decision. Evidence now sheds light on the importance of autophagy induced by cancer radiotherapy. Traditional view considers radiation can directly or indirectly damage DNA which can activate DNA damage the repair signaling pathway, a large number of proteins participating in DNA damage repair signaling pathway such as p53, ATM, PARP1, FOXO3a, mTOR and SIRT1 involved in autophagy regulation. However, emerging recent evidence suggests radiation can also cause injury to extranuclear targets such as plasma membrane, mitochondria and endoplasmic reticulum (ER) and induce accumulation of ceramide, ROS, and Ca2+ concentration which activate many signaling pathways to modulate autophagy...
October 5, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27729194/vcp-inhibitors-induce-endoplasmic-reticulum-stress-cause%C3%A2-cell-cycle-arrest-trigger-caspase-mediated-cell-death%C3%A2-and-synergistically-kill-ovarian-cancer-cells-in-combination-with-salubrinal
#13
Prabhakar Bastola, Lisa Neums, Frank J Schoenen, Jeremy Chien
Valosin-containing protein (VCP) or p97, a member of AAA-ATPase protein family, has been associated with various cellular functions including endoplasmic reticulum-associated degradation (ERAD), Golgi membrane reassembly, autophagy, DNA repair, and cell division. Recent studies identified VCP and ubiquitin proteasome system (UPS) as synthetic lethal targets in ovarian cancer. Here, we describe the preclinical activity of VCP inhibitors in ovarian cancer. Results from our studies suggest that quinazoline-based VCP inhibitors initiate G1 cell cycle arrest, attenuate cap-dependent translation and induce programmed cell death via the intrinsic and the extrinsic modes of apoptosis...
September 28, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27708237/proteomic-identification-of-the-lactate-dehydrogenase-a-in-a-radioresistant-prostate-cancer-xenograft-mouse-model-for-improving-radiotherapy
#14
Jingli Hao, Peter Graham, Lei Chang, Jie Ni, Valerie Wasinger, Julia Beretov, Junli Deng, Wei Duan, Joseph Bucci, David Malouf, David Gillatt, Yong Li
Radioresistance is a major challenge for prostate cancer (CaP) metastasis and recurrence after radiotherapy. This study aimed to identify potential protein markers and signaling pathways associated with radioresistance using a PC-3 radioresistant (RR) subcutaneous xenograft mouse model and verify the radiosensitization effect from a selected potential candidate. PC-3RR and PC-3 xenograft tumors were established and differential protein expression profiles from two groups of xenografts were analyzed using liquid chromatography tandem-mass spectrometry...
September 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27694690/suppression-of-pc-1-prlz-sensitizes-prostate-cancer-cells-to-ionizing-radiation-by-attenuating-dna-damage-repair-and-inducing-autophagic-cell-death
#15
Zeng-Fu Shang, Qiang Wei, Lan Yu, Fang Huang, Bei-Bei Xiao, Hongtao Wang, Man Song, Li Wang, Jianguang Zhou, Jian Wang, Shanhu Li
Radiotherapy is promising and effective for treating prostate cancer but the addition of a tumor cell radiosensitizer would improve therapeutic outcomes. PC-1/PrLZ, a TPD52 protein family member is frequently upregulated in advanced prostate cancer cells and may be a biomarker of aggressive prostate cancer. Therefore, we investigated the potential role of PC-1/PrLZ for increasing radioresistance in human prostate cancer cell lines. Growth curves and survival assays after g-ray irradiation confirmed that depletion of endogenous PC-1/PrLZ significantly increased prostate cancer cell radiosensitivity...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27684057/proteomic-profiling-reveals-the-induction-of-upr-in-addition-to-dna-damage-response-in-hela-cells-treated-with-the-thiazolo-5-4-b-quinoline-derivative-d3clp
#16
José Carlos Páez-Franco, Ignacio González-Sánchez, Nora A Gutiérrez-Nájera, Lilián G Valencia-Turcotte, Alfonso Lira-Rocha, Marco A Cerbón, Rogelio Rodríguez-Sotres
9-[(3-chloro)phenylamine]-2-[3-(diethylamine)propylamine]thiazolo[5,4-b]quinolone (D3ClP) is a bioisostere of N-(4-(acridin-9-ylamino)-3-methoxyphenyl)methanesulfonamide (m-AMSA) a DNA topoisomerase II inhibitor with proven cytotoxic activity and known to induce DNA damage and apoptotic cell death in K562 cells. However, recent evidence is not consistent with DNA topoisomerase II (DNA TOP2) as the primary target of D3ClP, in contrast to m-AMSA. We provide evidence of histone γH2AX phosphorylation at Ser135 in HeLa cells treated with D3ClP, a marker of DNA double strand repair through Mre11-Rad50-Nbs1 (MRN) pathway...
September 29, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27677401/the-role-of-rad51-in-safeguarding-mitochondrial-activity-during-the-meiotic-cell-cycle-in-mammalian-oocytes
#17
Kyeoung-Hwa Kim, Ji-Hoon Park, Eun-Young Kim, Jung-Jae Ko, Kyung-Soon Park, Kyung-Ah Lee
Rad51 is a conserved eukaryotic protein that mediates the homologous recombination repair of DNA double-strand breaks that occur during mitosis and meiosis. In addition, Rad51 promotes mitochondrial DNA synthesis when replication stress is increased. Rad51 also regulates cell cycle progression by preserving the G2/M transition in embryonic stem cells. In this study, we report a novel function of Rad51 in regulating mitochondrial activity during in vitro maturation of mouse oocytes. Suppression of Rad51 by injection of Rad51 dsRNA into germinal vesicle-stage oocytes resulted in arrest of meiosis in metaphase I...
September 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27644442/chloroquine-an-autophagy-inhibitor-potentiates-the-radiosensitivity-of-glioma-initiating-cells-by-inhibiting-autophagy-and-activating-apoptosis
#18
Hongxing Ye, Mantao Chen, Fei Cao, Hongguang Huang, Renya Zhan, Xiujue Zheng
BACKGROUND: Glioblastoma is refractory to conventional treatment, which is combined of surgery, chemotherapy and radiotherapy. Recent studies have shown that glioma initiating cells (GICs) contribute to tumorigenesis and radioresistance. Recently, other studies showed that the GICs use the autophagy as the major pathway to survive. Chloroquine, an anti-malarial chemical, is an autophagic inhibitor which blocks autophagosome fusion with lysosome and slows down lysosomal acidification. The aim of this study was to explore the mechanisms of chloroquine on the radiosensitivity of GICs...
September 20, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27572850/mtor-signaling-plays-a-critical-role-in-the-defects-observed-in-muscle-derived-stem-progenitor-cells-isolated-from-a-murine-model-of-accelerated-aging
#19
Koji Takayama, Yohei Kawakami, Mitra Lavasani, Xiaodong Mu, James H Cummins, Takashi Yurube, Ryosuke Kuroda, Masahiro Kurosaka, Freddie H Fu, Paul D Robbins, Laura J Niedernhofer, Johnny Huard
Mice expressing reduced levels of ERCC1-XPF (Ercc1(-/Δ) mice) demonstrate premature age-related changes due to their reduced capability to repair DNA damage. Muscle-derived stem/progenitor cells (MDSPCs) isolated from Ercc1(-/Δ) mice demonstrated an impaired capacity for cell differentiation. The mammalian target of rapamycin (mTOR) is a critical regulator of cell growth in response to the availability of nutrients, hormones and oxygen levels. Inhibition of the mTOR pathway has been shown to extend the lifespans of several different species...
August 30, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/27469198/age-dependent-neuroprotective-effects-of-medhya-rasayana-prepared-from-clitoria-ternatea-linn-in-stress-induced-rat-brain
#20
Kothanahalli S Raghu, Bhanuvalli R Shamprasad, Kabekkodu S Prasada, Puspendu Paladhi, Manjunath B Joshi, Marthandavarma S Valiathan, Kanive P Guruprasad, Kapaettu Satyamoorthy
ETHNOPHARMACOLOGICAL RELEVANCE: Indian traditional medicinal system in Ayurveda suggests several preparations, known as medhya rasayanas, of diverse plant origin to enhance the health in general, reduce stress and improve brain function in particular during ageing. These effects in the context of contemporary knowledge and the underlying mechanisms are not clearly understood. Autophagy and DNA damage induced repair are inter-related quintessential pathways and are significantly altered during stress and ageing...
July 25, 2016: Journal of Ethnopharmacology
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