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https://www.readbyqxmd.com/read/29051947/pre-steady-state-kinetic-analysis-of-damage-recognition-by-human-single-strand-selective-monofunctional-uracil-dna-glycosylase-smug1
#1
Alexandra A Kuznetsova, Danila A Iakovlev, Inna V Misovets, Alexander A Ishchenko, Murat K Saparbaev, Nikita A Kuznetsov, Olga S Fedorova
In all organisms, DNA glycosylases initiate base excision repair pathways resulting in removal of aberrant bases from DNA. Human SMUG1 belongs to the superfamily of uracil-DNA glycosylases catalyzing the hydrolysis of the N-glycosidic bond of uridine and uridine lesions bearing oxidized groups at C5: 5-hydroxymethyluridine (5hmU), 5-formyluridine (5fU), and 5-hydroxyuridine (5hoU). An apurinic/apyrimidinic (AP) site formed as the product of an N-glycosylase reaction is tightly bound to hSMUG1, thus inhibiting the downstream action of AP-endonuclease APE1...
October 20, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/29039534/apurinic-apyrimidinic-endonuclease-1-ape1-contributes-to-resveratrol%C3%A2-induced-neuroprotection-against-oxygen%C3%A2-glucose-deprivation-and-re%C3%A2-oxygenation-injury-in-ht22-cells-involvement-in-reducing-oxidative-dna-damage
#2
Jiao-Ying Jia, Zhi-Gang Tan, Min Liu, Yu-Gang Jiang
Resveratrol, a naturally occurring polyphenolic compound, exhibits a neuroprotective role in models of central nervous system diseases, including cerebral ischemia/reperfusion injury. Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme that contributes to base excision repair of oxidative DNA damage and redox activation of transcription factors, associated with neuronal survival against hypoxic‑ischemic injury. It was hypothesized that resveratrol protects HT22 cells against oxygen‑glucose deprivation and re‑oxygenation (OGD/R)‑induced injuries through upregulation of APE1...
October 17, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29036362/cux1-stimulates-ape1-enzymatic-activity-and-increases-the-resistance-of-glioblastoma-cells-to-the-mono-alkylating-agent-temozolomide
#3
Simran Kaur, Zubaidah M Ramdzan, Marie-Christine Guiot, Li Li, Lam Leduy, Dindial Ramotar, Siham Sabri, Bassam Abdulkarim, Alain Nepveu
Background: CUX1, which encodes an auxiliary factor in base excision repair, resides on 7q22.1, the most frequently and highly amplified chromosomal region in glioblastomas. The resistance of glioblastoma cells to the mono-alkylating agent temozolomide is determined to some extent by the activity of the apurinic/apyrimidinic endonuclease 1, APE1. Methods: To monitor the effect of CUX1 and its CUT domains on APE1 activity, DNA repair assays were performed with purified proteins and cell extracts...
September 26, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29035403/-polymorphism-of-genes-encoding-proteins-of-dna-repair-vs-occupational-and-environmental-exposure-to-lead-arsenic-and-pesticides
#4
REVIEW
Karol Bukowski, Katarzyna Woźniak
Genetic polymorphism is associated with the occurrence of at least 2 different alleles in the locus with a frequency higher than 1% in the population. Among polymorphisms we can find single nucleotide polymorphism (SNP) and polymorphism of variable number of tandem repeats. The presence of certain polymorphisms in genes encoding DNA repair enzymes is associated with the speed and efficiency of DNA repair and can protect or expose humans to the effects provoked by xenobiotics. Chemicals, such as lead, arsenic pesticides are considered to exhibit strong toxicity...
October 12, 2017: Medycyna Pracy
https://www.readbyqxmd.com/read/28986522/mammalian-ape1-controls-mirna-processing-and-its-interactome-is-linked-to-cancer-rna-metabolism
#5
Giulia Antoniali, Fabrizio Serra, Lisa Lirussi, Mikiei Tanaka, Chiara D'Ambrosio, Shiheng Zhang, Slobodanka Radovic, Emiliano Dalla, Yari Ciani, Andrea Scaloni, Mengxia Li, Silvano Piazza, Gianluca Tell
Mammalian apurinic/apyrimidinic endonuclease 1 is a DNA repair enzyme involved in genome stability and expression of genes involved in oxidative stress responses, tumor progression and chemoresistance. However, the molecular mechanisms underlying the role of apurinic/apyrimidinic endonuclease 1 in these processes are still unclear. Recent findings point to a novel role of apurinic/apyrimidinic endonuclease 1 in RNA metabolism. Through the characterization of the interactomes of apurinic/apyrimidinic endonuclease 1 with RNA and other proteins, we demonstrate here a role for apurinic/apyrimidinic endonuclease 1 in pri-miRNA processing and stability via association with the DROSHA-processing complex during genotoxic stress...
October 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28980865/morphometric-analysis-of-autophagy-related-structures-in-saccharomyces-cerevisiae
#6
Tatsuya Kawaoka, Shinsuke Ohnuki, Yoshikazu Ohya, Kuninori Suzuki
When macroautophagy (autophagy) is induced by nutrient starvation or rapamycin treatment, Atg (autophagy-related) proteins are assembled at a restricted region close to the vacuole. Subsequently, the phagophore expands to form a closed autophagosome. In Saccharomyces cerevisiae cells overexpressing precursor Ape1 (prApe1), a specific autophagosome cargo protein, the phagophore can be visualized as a cup-shaped structure labeled with green fluorescent protein (GFP)-tagged Atg8. Previously, our group has shown that the maximum length of GFP-Atg8-labeled structures reflects the magnitude of bulk autophagy...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28977421/abasic-and-oxidized-ribonucleotides-embedded-in-dna-are-processed-by-human-ape1-and-not-by-rnase-h2
#7
Matilde Clarissa Malfatti, Sathya Balachander, Giulia Antoniali, Kyung Duk Koh, Christine Saint-Pierre, Didier Gasparutto, Hyongi Chon, Robert J Crouch, Francesca Storici, Gianluca Tell
Ribonucleoside 5'-monophosphates (rNMPs) are the most common non-standard nucleotides found in DNA of eukaryotic cells, with over 100 million rNMPs transiently incorporated in the mammalian genome per cell cycle. Human ribonuclease (RNase) H2 is the principal enzyme able to cleave rNMPs in DNA. Whether RNase H2 may process abasic or oxidized rNMPs incorporated in DNA is unknown. The base excision repair (BER) pathway is mainly responsible for repairing oxidized and abasic sites into DNA. Here we show that human RNase H2 is unable to process an abasic rNMP (rAP site) or a ribose 8oxoG (r8oxoG) site embedded in DNA...
August 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28965839/dna-damage-mediates-changes-in-neuronal-sensitivity-induced-by-the-inflammatory-mediators-mcp-1-and-lps-and-can-be-reversed-by-enhancing-the-dna-repair-function-of-ape1
#8
Jill C Fehrenbacher, Chunlu Guo, Mark R Kelley, Michael R Vasko
Although inflammation-induced peripheral sensitization oftentimes resolves as an injury heals, this sensitization can be pathologically maintained and contribute to chronic inflammatory pain. Numerous inflammatory mediators increase the production of reactive oxygen (ROS) and nitrogen species (RNS) during inflammation and in animal models of chronic neuropathic pain. Our previous studies demonstrate that ROS/RNS and subsequent DNA damage mediate changes in neuronal sensitivity induced by anticancer drugs and by ionizing radiation in sensory neurons, thus we investigated whether inflammation and inflammatory mediators also could cause DNA damage in sensory neurons and whether that DNA damage alters neuronal sensitivity...
September 28, 2017: Neuroscience
https://www.readbyqxmd.com/read/28946662/ape1-ref-1-inhibits-phosphate-induced-calcification-and-osteoblastic-phenotype-changes-in-vascular-smooth-muscle-cells
#9
Ki Mo Lee, Eun Ok Lee, Yu Ran Lee, Hee Kyoung Joo, Myoung Soo Park, Cuk-Seong Kim, Sunga Choi, Jin-Ok Jeong, Byeong Hwa Jeon
Vascular calcification plays a role in the pathogenesis of atherosclerosis, diabetes, and chronic kidney disease; however, the role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in inorganic phosphate (Pi)-induced vascular smooth muscle cell (VSMC) calcification remains unknown. In this study, we investigated the possible role of APE1/Ref-1 in Pi-induced VSMC calcification. We observed that Pi decreased endogenous APE1/Ref-1 expression and promoter activity in VSMCs, and that adenoviral overexpression of APE1/Ref-1 inhibited Pi-induced calcification in VSMCs and in an ex vivo organ culture of a rat aorta...
September 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28946035/dna-repair-enzyme-ape1-from-evolutionarily-ancient-hydra-reveals-redox-activity-exclusively-found-in-mammalian-ape1
#10
Komal Pekhale, Gauri Haval, Nusrat Perween, Giulia Antoniali, Gianluca Tell, Surendra Ghaskadbi, Saroj Ghaskadbi
Only mammalian apurinic/apyrimidinic endonuclease1 (APE1) has been reported to possess both DNA repair and redox activities. C terminal of the protein is required for base excision repair, while the redox activity resides in the N terminal due to cysteine residues at specific positions. APE1s from other organisms studied so far lack the redox activity in spite of having the N terminal domain. We find that APE1 from the Cnidarian Hydra exhibits both endonuclease and redox activities similar to mammalian APE1...
September 18, 2017: DNA Repair
https://www.readbyqxmd.com/read/28938675/ape1-overexpression-is-associated-with-poor-survival-in-patients-with-solid-tumors-a-meta-analysis
#11
Chun-Ling Yuan, Fan He, Jia-Zhou Ye, Hui-Ni Wu, Jin-Yan Zhang, Zhi-Hui Liu, Yong-Qiang Li, Xiao-Ling Luo, Yan Lin, Rong Liang
APE1 is known as a key mediator of DNA damage repair pathways, and its clinical significance in different types of cancer is well studied. Herein, we performed a meta-analysis to determine the association of APE1 expression and survival in different types of solid cancer. We searched all eligible publications in PubMed, Web of Science and Embase platforms from inception to January 2017 and found 15 relevant manuscripts. Overall survival (OS), 12- and 36-month survival rates, and hazard ratios (HRs) were extracted and analyzed...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28922540/ape1-ref-1-knockdown-in-pancreatic-ductal-adenocarcinoma-characterizing-gene-expression-changes-and-identifying-novel-pathways-using-single-cell-rna-sequencing
#12
Fenil Shah, Emery Goossens, Nadia M Atallah, Michelle Grimard, Mark R Kelley, Melissa L Fishel
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1 or APE1) is a multifunctional protein that regulates numerous transcription factors associated with cancer-related pathways. Because APE1 is essential for cell viability, generation of APE1 knockout cell lines and determining a comprehensive list of genes regulated by APE1 has not been possible. To circumvent this challenge, we utilized single-cell RNA Sequencing to identify differentially expressed genes in relation to APE1 protein levels within the cell...
September 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28887667/ape1-modulates-cellular-responses-to-organophosphate-pesticide-induced-oxidative-damage-in-non-small-cell-lung-carcinoma-a549-cells
#13
Shweta Thakur, Monisha Dhiman, Anil K Mantha
Monocrotophos (MCP) and chlorpyrifos (CP) are widely used organophosphate pesticides (OPPs), speculated to be linked with human pathologies including cancer. Owing to the fact that lung cells are most vulnerable to the environmental toxins, the development and progression of lung cancer can be caused by the exposure of OPPs. The present study investigates the oxidative DNA damage response evoked by MCP and CP in human non-small cell lung carcinoma A549 cells. A549 cells were exposed to MCP and CP; cytotoxicity and reactive oxygen species (ROS) generation were measured to select the non-toxic dose...
September 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28881698/reduction-oxidation-pathways-involved-in-cancer-development-a-systematic-review-of-literature-reviews
#14
REVIEW
Xīn Gào, Ben Schöttker
Oxidative stress results from an imbalance of the reactive oxygen species/reactive nitrogen species (ROS/RNS) production and the oxidants defense system. Extensive research during the last decades has revealed that oxidative stress can mediate cancer initiation and development by leading not only to molecular damage but also to a disruption of reduction-oxidation (redox) signaling. In order to provide a global overview of the redox signaling pathways, which play a role in cancer formation, we conducted a systematic literature search in PubMed and ISI Web of Science and identified 185 relevant reviews published in the last 10 years...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28861684/curcumin-revitalizes-amyloid-beta-25-35-induced-and-organophosphate-pesticides-pestered-neurotoxicity-in-sh-sy5y-and-imr-32-cells-via-activation-of-ape1-and-nrf2
#15
Bibekananda Sarkar, Monisha Dhiman, Sunil Mittal, Anil K Mantha
Amyloid beta (Aβ) peptide deposition is the primary cause of neurodegeneration in Alzheimer's disease (AD) pathogenesis. Several reports point towards the role of pesticides in the AD pathogenesis, especially organophosphate pesticides (OPPs). Monocrotophos (MCP) and Chlorpyrifos (CP) are the most widely used OPPs. In this study, the role of MCP and CP in augmenting the Aβ-induced oxidative stress associated with the neurodegeneration in AD has been assessed in human neuroblastoma IMR-32 and SH-SY5Y cell lines...
August 31, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28854357/neil3-repairs-telomere-damage-during-s-phase-to-secure-chromosome-segregation-at-mitosis
#16
Jia Zhou, Jany Chan, Marie Lambelé, Timur Yusufzai, Jason Stumpff, Patricia L Opresko, Markus Thali, Susan S Wallace
Oxidative damage to telomere DNA compromises telomere integrity. We recently reported that the DNA glycosylase NEIL3 preferentially repairs oxidative lesions in telomere sequences in vitro. Here, we show that loss of NEIL3 causes anaphase DNA bridging because of telomere dysfunction. NEIL3 expression increases during S phase and reaches maximal levels in late S/G2. NEIL3 co-localizes with TRF2 and associates with telomeres during S phase, and this association increases upon oxidative stress. Mechanistic studies reveal that NEIL3 binds to single-stranded DNA via its intrinsically disordered C terminus in a telomere-sequence-independent manner...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28852018/ape1-guides-dna-repair-pathway-choice-that-is-associated-with-drug-tolerance-in-glioblastoma
#17
Thomas Ströbel, Sibylle Madlener, Serkan Tuna, Sarah Vose, Tonny Lagerweij, Thomas Wurdinger, Klemens Vierlinger, Adelheid Wöhrer, Brendan D Price, Bruce Demple, Okay Saydam, Nurten Saydam
Ape1 is the major apurinic/apyrimidinic (AP) endonuclease activity in mammalian cells, and a key factor in base-excision repair of DNA. High expression or aberrant subcellular distribution of Ape1 has been detected in many cancer types, correlated with drug response, tumor prognosis, or patient survival. Here we present evidence that Ape1 facilitates BRCA1-mediated homologous recombination repair (HR), while counteracting error-prone non-homologous end joining of DNA double-strand breaks. Furthermore, Ape1, coordinated with checkpoint kinase Chk2, regulates drug response of glioblastoma cells...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28846606/the-emerging-role-of-glp-1-receptors-in-dna-repair-implications-in-neurological-disorders
#18
REVIEW
Jenq-Lin Yang, Wei-Yu Chen, Shang-Der Chen
Glucagon-like peptide-1 (GLP-1) is originally found as a metabolic hormone (incretin) that is able to regulate blood-glucose levels via promoting synthesis and secretion of insulin. GLP-1 and many analogues are approved for treatment of type II diabetes. Accumulating results imply that GLP-1 performs multiple functions in various tissues and organs beyond regulation of blood-glucose. The neuroprotective function of GLP-1 has been extensively explored during the past two decades. Three of our previous studies have shown that apurinic/apyrimidinic endonuclease 1 (APE1) is the only protein of the base excision repair (BER) pathway able to be regulated by oxidative stress or exogenous stimulations in rat primary cortical neurons...
August 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28839218/rs1760944-polymorphism-in-the-ape1-region-is-associated-with-risk-and-prognosis-of-osteosarcoma-in-the-chinese-han-population
#19
Xing Xiao, Yun Yang, Yanjun Ren, Debo Zou, Kaining Zhang, Yingguang Wu
The effects of single nucleotide polymorphisms (SNPs) at APE1 have been investigated in several types of cancer. However, no reports of the association of APE1 polymorphisms with osteosarcoma (OS) have been published. The present study was designed to determine whether APE1 polymorphisms (rs1130409, rs1760944, rs1760941, rs2275008, rs17111750) are associated with OS. A 2-stage case-control study was performed in a total of 378 OS patients and 616 normal controls. Individuals carrying TG and GG genotypes had significantly lower risk of developing OS than those with the WT genotype TT at rs1760944 (OR = 0...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28830792/functional-analysis-of-the-selective-autophagy-related-gene-acatg11-in-acremonium-chrysogenum
#20
Jiajia Liu, Tianchao Hao, Pengjie Hu, Yuanyuan Pan, Xuejun Jiang, Gang Liu
Autophagy is a highly conserved degradation system in eukaryotes. Selective autophagy is used for the degradation of selective cargoes. Selective autophagic processes of yeast include pexophagy, mitophagy, and cytoplasm-to-vacuole targeting (Cvt) pathway in which particular vacuolar proteins, such asaminopeptidase I (Ape1), are selectively transported to vacuoles. However, the physiological role of selective autophagy remains elusive in filamentous fungi. ATG11 family proteins asa basic scaffold are essential for most selective autophagy pathways in yeast...
October 2017: Fungal Genetics and Biology: FG & B
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