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BER pathway

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https://www.readbyqxmd.com/read/29352041/stress-signaling-jnk2-crosstalk-with-camkii-underlies-enhanced-atrial-arrhythmogenesis
#1
Jiajie Yan, Weiwei Zhao, Justin K Thomson, Xianlong Gao, Dominic M DeMarco, Elena Carrillo, Biyi Chen, Xiaomin Wu, Kenneth S Ginsburg, Mamdouh Bakhos, Donald M Bers, Mark E Anderson, Long-Sheng Song, Michael Fill, Xun Ai
Rationale: Atrial fibrillation (AF) is the most common arrhythmia and advanced age is an inevitable and predominant AF risk factor. However, the mechanisms that couple aging and AF propensity remain unclear, making targeted therapeutic interventions unattainable. Objective: To explore the functional role of an important stress-response c-Jun N-terminal kinase (JNK) in sarcoplasmic reticulum (SR) Ca2+ handling and consequently Ca2+-mediated atrial arrhythmias. Methods and Results: We employed a series of cutting-edge electrophysiological and molecular techniques, exploited the power of transgenic mouse models to detail the molecular mechanism, and verified its clinical applicability in parallel studies on donor human hearts...
January 19, 2018: Circulation Research
https://www.readbyqxmd.com/read/29342113/mitochondria-oxidative-stress-and-the-kynurenine-system-with-a-focus-on-ageing-and-neuroprotection
#2
REVIEW
Katalin Sas, Elza Szabó, László Vécsei
In this review, the potential causes of ageing are discussed. We seek to gain insight into the main physiological functions of mitochondria and discuss alterations in their function and the genome, which are supposed to be the central mechanisms in senescence. We conclude by presenting the potential modulating role of the kynurenine pathway in the ageing processes. Mitochondrial dynamics are supposed to have important physiological roles in maintaining cell homeostasis. During ageing, a decrease in mitochondrial dynamics was reported, potentially compromising the function of mitochondria...
January 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29305386/the-chromatin-remodeler-isw1-prevents-cag-repeat-expansions-during-transcription-in-saccharomyces-cerevisiae
#3
Melissa R Koch, Nealia C M House, Casey M Cosetta, Robyn M Jong, Christelle G Salomon, Cailin E Joyce, Elliot A Philips, Xiaofeng A Su, Catherine H Freudenreich
CAG/CTG trinucleotide repeats are unstable sequences that are difficult to replicate, repair, and transcribe due to their structure-forming nature. CAG repeats strongly position nucleosomes, however little is known about the chromatin remodeling needed to prevent repeat instability. In a Saccharomyces cerevisiae model system with CAG repeats carried on a yeast artificial chromosome, we discovered that the chromatin remodeler Isw1 is required to prevent CAG repeat expansions during transcription. CAG repeat expansions in the absence of Isw1 were dependent on both transcription-coupled repair (TCR) and base excision repair (BER)...
January 5, 2018: Genetics
https://www.readbyqxmd.com/read/29244109/gadd45a-promotes-active-dna-demethylation-of-the-mmp-9-promoter-via-base-excision-repair-pathway-in-ages-treated-keratinocytes-and-in-diabetic-male-rat-skin
#4
Liyan Zhou, Wei Wang, Chuan Yang, Tingting Zeng, Mengdie Hu, Xiaoyi Wang, Na Li, Kan Sun, Chuan Wang, Jing Zhou, Meng Ren, Li Yan
Diabetes elevates matrix metalloproteinase-9 (MMP-9) levels in the skin and its keratinocytes, and activated MMP-9 impairs skin wound healing. Epigenetic regulation of the DNA methylation status within the MMP-9 promoter plays an important role in the alteration of MMP-9 expression. Our aim was to investigate the role and mechanism of growth arrest and DNA damage-inducible 45a (GADD45a), a well-known DNA demethylation regulatory protein that mediates DNA methylation, in the regulation of MMP-9 expression. In this study, we showed that GADD45a was markedly upregulated in skin tissues from patients with diabetic foot ulcers, in diabetic rats and in human keratinocyte (HaCaT) cells exposed to advanced glycation end products (AGEs)...
December 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/29202295/constitutive-map-kinase-activation-suppresses-germline-apoptosis-in-nth-1-dna-glycosylase-deficient-c-elegans
#5
Henok Kassahun, Tanima SenGupta, Alfonso Schiavi, Silvia Maglioni, Hanne K Skjeldam, Katarzyna Arczewska, Nicole L Brockway, Suzanne Estes, Lars Eide, Natascia Ventura, Hilde Nilsen
Oxidation of DNA bases, an inevitable consequence of oxidative stress, requires the base excision repair (BER) pathway for repair. Caenorhabditis elegans is a well-established model to study phenotypic consequences and cellular responses to oxidative stress. To better understand how BER affects phenotypes associated with oxidative stress, we characterised the C. elegans nth-1 mutant, which lack the only DNA glycosylase dedicated to repair of oxidative DNA base damage, the NTH-1 DNA glycosylase. We show that nth-1 mutants have mitochondrial dysfunction characterised by lower mitochondrial DNA copy number, reduced mitochondrial membrane potential, and increased steady-state levels of reactive oxygen species...
November 29, 2017: DNA Repair
https://www.readbyqxmd.com/read/29185360/role-of-metformin-on-base-excision-repair-pathway-in-p53-wild-type-h2009-and-hepg2-cancer-cells
#6
I D Turacli, T Candar, E B Yuksel, S Demirtas
The antidiabetic agent metformin was shown to further possess chemopreventive and chemotherapeutic effects against cancer. Despite the advances, the underlying molecular mechanisms involved in decreasing tumor formation are still unclear. The understanding of the participation of oxidative stress in the action mechanism of metformin and its related effects on p53 and on DNA base excision repair (BER) system can help us to get closer to solve metformin puzzle in cancer. We investigated the effects of metformin in HepG2 and H2009 cells, verifying cytotoxicity, oxidative stress, antioxidant status, and DNA BER system...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29171825/guardians-of-the-mycobacterial-genome-a-review-on-dna-repair-systems-in-mycobacterium-tuberculosis
#7
Amandeep Singh
The genomic integrity of Mycobacterium tuberculosis is continuously threatened by the harsh survival conditions inside host macrophages, due to immune and antibiotic stresses. Faithful genome maintenance and repair must be accomplished under stress for the bacillus to survive in the host, necessitating a robust DNA repair system. The importance of DNA repair systems in pathogenesis is well established. Previous examination of the M. tuberculosis genome revealed homologues of almost all the major DNA repair systems, i...
November 24, 2017: Microbiology
https://www.readbyqxmd.com/read/29156789/xrcc1-mediated-the-development-of-cervival-cancer-through-a-novel-sp1-krox-20-swich
#8
Qingtao Meng, Shizhi Wang, Weiyan Tang, Shenshen Wu, Na Gao, Chengcheng Zhang, Xiaoli Cao, Xiaobo Li, Zhengdong Zhang, Michael Aschner, Hua Jin, Yue Huang, Rui Chen
Cervical cancer is the second leading cause of mortality among women. Impairment of the base excision repair (BER) pathway is one of the major causes of the initiation and progression of cervical cancer. However, whether the polymorphisms of the BER pathway components (i.e., HOGG1, XRCC1, ADPRT, and APE1) can affect the risk of cervical cancer remains unknown. Herein, we applied a hospital-based case-control study covering two independent cohorts and a subsequent functional assay to determine the roles of the single nucleotide polymorphisms (SNPs) of the BER pathway genes in cervical cancer...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156764/the-neil1-g83d-germline-dna-glycosylase-variant-induces-genomic-instability-and-cellular-transformation
#9
Heather A Galick, Carolyn G Marsden, Scott Kathe, Julie A Dragon, Lindsay Volk, Antonia A Nemec, Susan S Wallace, Aishwarya Prakash, Sylvie Doublié, Joann B Sweasy
Base excision repair (BER) is a key genome maintenance pathway. The NEIL1 DNA glycosylase recognizes oxidized bases, and likely removes damage in advance of the replication fork. The rs5745906 SNP of the NEIL1 gene is a rare human germline variant that encodes the NEIL1 G83D protein, which is devoid of DNA glycosylase activity. Here we show that expression of G83D NEIL1 in MCF10A immortalized but non-transformed mammary epithelial cells leads to replication fork stress. Upon treatment with hydrogen peroxide, we observe increased levels of stalled replication forks in cells expressing G83D NEIL1 versus cells expressing the wild-type (WT) protein...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156686/crosstalk-between-mismatch-repair-and-base-excision-repair-in-human-gastric-cancer
#10
Valeria Simonelli, Giuseppe Leuzzi, Giorgia Basile, Mariarosaria D'Errico, Paola Fortini, Annapaola Franchitto, Valentina Viti, Ashley R Brown, Eleonora Parlanti, Barbara Pascucci, Domenico Palli, Alessandro Giuliani, Fabio Palombo, Robert W Sobol, Eugenia Dogliotti
DNA repair gene expression in a set of gastric cancers suggested an inverse association between the expression of the mismatch repair (MMR) gene MLH1 and that of the base excision repair (BER) gene DNA polymerase β (Polβ). To gain insight into possible crosstalk of these two repair pathways in cancer, we analysed human gastric adenocarcinoma AGS cells over-expressing Polβ or Polβ active site mutants, alone or in combination with MLH1 silencing. Next, we investigated the cellular response to the alkylating agent methyl methanesulfonate (MMS) and the purine analogue 6-thioguanine (6-TG), agents that induce lesions that are substrates for BER and/or MMR...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152101/functional-network-analysis-of-gene-phenotype-connectivity-associated-with-temozolomide
#11
Jia Shi, Bo Dong, Peng Zhou, Wei Guan, Ya Peng
Rationale: Glioma has a poor survival rate in patients even with aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for treating glioma, but TMZ treatment consistently leads to high resistance. Aim: To investigate the underlying mechanisms of TMZ action with new therapeutic regimens in glioma. Methods and results: The biological effects of TMZ mainly depend on the three following DNA repair systems: methylguanine methyltransferase (MGMT), mismatch repair (MMR) and base excision repair (BER)...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29122935/in-vivo-measurements-of-interindividual-differences-in-dna-glycosylases-and-ape1-activities
#12
Isaac A Chaim, Zachary D Nagel, Jennifer J Jordan, Patrizia Mazzucato, Le P Ngo, Leona D Samson
The integrity of our DNA is challenged with at least 100,000 lesions per cell on a daily basis. Failure to repair DNA damage efficiently can lead to cancer, immunodeficiency, and neurodegenerative disease. Base excision repair (BER) recognizes and repairs minimally helix-distorting DNA base lesions induced by both endogenous and exogenous DNA damaging agents. Levels of BER-initiating DNA glycosylases can vary between individuals, suggesting that quantitating and understanding interindividual differences in DNA repair capacity (DRC) may enable us to predict and prevent disease in a personalized manner...
November 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29118522/association-of-leukotrichia-in-vitiligo-and-asp148glu-polymorphism-of-apurinic-apyrimidinic-endonuclease-1
#13
A Fatih Aydin, İkbal Esen Aydıngöz, Semra Doğru-Abbasoğlu, Pervin Vural, Müjdat Uysal
Background: Oxidative stress and increased DNA damage have been implicated in the etiopathogenesis of vitiligo. Oxidative DNA damage is mainly repaired by the base excision repair (BER) pathway. Aim: We sought to determine whether polymorphisms in DNA repair genes may have a role in the pathogenesis of vitiligo. Materials and Methods: We conducted a study including 100 patients with vitiligo and age- and sex-matched 193 control subjects to examine the role of single-nucleotide polymorphisms of BER genes, human 8-oxoG DNA N-glycosylase 1 (codon 326), apurinic/apyrimidinic endonuclease 1 (APE1) (codon 148), and X-ray repair cross-complementing group 1 (codon 399) as risk factors for vitiligo...
October 2017: International Journal of Trichology
https://www.readbyqxmd.com/read/29112132/autophagy-roles-in-the-modulation-of-dna-repair-pathways
#14
REVIEW
Luciana R Gomes, Carlos F M Menck, Giovana S Leandro
Autophagy and DNA repair are biological processes vital for cellular homeostasis maintenance and when dysfunctional, they lead to several human disorders including premature aging, neurodegenerative diseases, and cancer. The interchange between these pathways is complex and it may occur in both directions. Autophagy is activated in response to several DNA lesions types and it can regulate different mechanisms and molecules involved in DNA damage response (DDR), such as cell cycle checkpoints, cell death, and DNA repair...
November 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29108254/the-impacts-of-genetic-polymorphisms-in-genes-of-base-excision-repair-pathway-on-the-efficacy-and-acute-toxicities-of-chemo-radiotherapy-in-patients-with-nasopharyngeal-carcinoma
#15
Jing Wang, Chengxian Guo, Xiaochang Gong, Fan Ao, Yuling Huang, Lihua Huang, Yiqiang Tang, Chunling Jiang, Xiaoxue Xie, Qing Dong, Min Huang, Jingao Li
Purpose: To explore whether polymorphisms in base excision repair (BER) pathway genes are predictors of (chemo)radiotherapy outcome in patients with nasopharyngeal carcinoma (NPC). Methods: We genotyped five potentially functional single nucleotide polymorphisms (SNPs) of three genes in the BER pathway in 174 NPC patients who were treated with (chemo)radiotherapy. Sequenom MassArray was used for SNPs analysis. The efficacy at the end of radiotherapy and at 3 months after radiotherapy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST)...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29105096/nthl1-and-mutyh-polyposis-syndromes-two-sides-of-the-same-coin
#16
REVIEW
Robbert D A Weren, Marjolijn J L Ligtenberg, Ad Geurts van Kessel, Richarda M De Voer, Nicoline Hoogerbrugge, Roland P Kuiper
It is well-established now that germline genomic aberrations can underlie high-penetrant familial polyposis and colorectal cancer syndromes, but a genetic cause has not yet been found for the major proportion of patients with polyposis. Since next generation sequencing has become widely accessible, several novel, but rare, high-penetrant risk factors for adenomatous polyposis have been identified, all operating in pathways responsible for genomic maintenance and DNA repair. One of these is the base excision repair (BER) pathway...
November 3, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29089537/dna-ligase-c-and-prim-polc-participate-in-base-excision-repair-in-mycobacteria
#17
Przemysław Płociński, Nigel C Brissett, Julie Bianchi, Anna Brzostek, Małgorzata Korycka-Machała, Andrzej Dziembowski, Jarosław Dziadek, Aidan J Doherty
Prokaryotic Ligase D is a conserved DNA repair apparatus processing DNA double-strand breaks in stationary phase. An orthologous Ligase C (LigC) complex also co-exists in many bacterial species but its function is unknown. Here we show that the LigC complex interacts with core BER enzymes in vivo and demonstrate that together these factors constitute an excision repair apparatus capable of repairing damaged bases and abasic sites. The polymerase component, which contains a conserved C-terminal structural loop, preferentially binds to and fills-in short gapped DNA intermediates with RNA and LigC ligates the resulting nicks to complete repair...
November 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/29055350/berberine-alleviates-oxidative-stress-in-rats-with-osteoporosis-through-receptor-activator-of-nuclear-factor-%C3%AE%C2%BA-b-receptor-activator-of-nuclear-factor-kappa-b-ligand-osteoprotegerin-rank-rankl-opg-pathway
#18
Xiao-Feng He, Long Zhang, Chun-Hua Zhang, Con-Ran Zhao, Heng Li, Ling-Fei Zhang, Guo-Feng Tian, Ming-Feng Guo, Zheng Dai, Fu-Ge Sui
Previous studies suggested that oxidative stress is related to the onset and development of osteoporosis. Moreover, it was demonstrated that berberine has a protective effect against oxidative stress-induced injuries. In this study, we aimed to investigate the effect and mechanism of action of berberine on rats with induced osteoporosis. Sixty 8-week-old female Wistar rats were randomly divided into the following 6 groups: control saline-treated, osteoporosis saline-treated, 3 osteoporosis berberine-treated groups (Ber 5, 10, and 20 mg/kg/body weight, respectively), and osteoporosis alendronate-treated (ALD) group...
October 22, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29031294/a-label-free-and-highly-sensitive-strategy-for-uracil-dna-glycosylase-activity-detection-based-on-stem-loop-primer-mediated-exponential-amplification-spea
#19
Wenfang Du, Junjie Li, Fubing Xiao, Ruqin Yu, Jianhui Jiang
Uracil-DNA glycosylase (UDG) plays essential roles in base excision repair (BER) pathway by eliminating uracil from DNA to sustain the genome integrity. Sensitive detection of UDG activity is of great significance in the study of many fundamental biochemical processes and clinical applications. We develop a label-free method for UDG activity detection using stem-loop primer-mediated exponential amplification (SPEA). In the presence of active UDG, the uracil base in helper hairpin probe (HP) can be excised to generate an abasic site (AP site), which can be cleaved by endonuclease IV (Endo IV) with a blocked primer released...
October 23, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29021553/development-of-a-cell-based-assay-for-measuring-base-excision-repair-responses
#20
Tyler Golato, Boris Brenerman, Daniel R McNeill, Jianfeng Li, Robert W Sobol, David M Wilson
Base excision repair (BER) is the predominant pathway for coping with most forms of hydrolytic, oxidative or alkylative DNA damage. Measuring BER capacity in living cells is valuable for both basic science applications and epidemiological studies, since deficiencies in this pathway have been associated with cancer susceptibility and other adverse health outcomes. At present, there is an ongoing effort to develop methods to effectively quantify the rate of BER as a whole. We present a variation of a previously described "Oligonucleotide Retrieval Assay" designed to measure DNA excision repair that is capable of quantifying the rate of repair of thymine glycol in a variety of human cells with a high degree of sensitivity...
October 11, 2017: Scientific Reports
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