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DNA DAMAGE AND REPAIR

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https://www.readbyqxmd.com/read/27911399/tools-to-study-the-role-of-architectural-protein-hmgb1-in-the-processing-of-helix-distorting-site-specific-dna-interstrand-crosslinks
#1
Anirban Mukherjee, Karen M Vasquez
High mobility group box 1 (HMGB1) protein is a non-histone architectural protein that is involved in regulating many important functions in the genome, such as transcription, DNA replication, and DNA repair. HMGB1 binds to structurally distorted DNA with higher affinity than to canonical B-DNA. For example, we found that HMGB1 binds to DNA interstrand crosslinks (ICLs), which covalently link the two strands of the DNA, cause distortion of the helix, and if left unrepaired can cause cell death. Due to their cytotoxic potential, several ICL-inducing agents are currently used as chemotherapeutic agents in the clinic...
November 10, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27910856/acquired-resistance-of-pancreatic-cancer-cells-to-cisplatin-is-multifactorial-with-cell-context-dependent-involvement-of-resistance-genes
#2
R Mezencev, L V Matyunina, G T Wagner, J F McDonald
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal of malignancies, in large measure, due to the propensity of PDAC cells to acquire resistance to chemotherapeutic agents. A better understanding of the molecular basis of acquired resistance is a major focus of contemporary PDAC research. We report here the results of a study to independently develop cisplatin resistance in two distinct parental PDAC cell lines, AsPC1 and BxPC3, and to subsequently examine the molecular mechanisms associated with the acquired resistance...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27909446/functional-toxicogenomic-profiling-expands-insight-into-modulators-of-formaldehyde-toxicity-in-yeast
#3
Matthew North, Brandon D Gaytán, Carlos Romero, Vanessa Y De La Rosa, Alex Loguinov, Martyn T Smith, Luoping Zhang, Chris D Vulpe
Formaldehyde (FA) is a commercially important chemical with numerous and diverse uses. Accordingly, occupational and environmental exposure to FA is prevalent worldwide. Various adverse effects, including nasopharyngeal, sinonasal, and lymphohematopoietic cancers, have been linked to FA exposure, prompting designation of FA as a human carcinogen by U.S. and international scientific entities. Although the mechanism(s) of FA toxicity have been well studied, additional insight is needed in regard to the genetic requirements for FA tolerance...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27908934/gata6-promotes-hair-follicle-progenitor-cell-renewal-by-genome-maintenance-during-proliferation
#4
Alex B Wang, Ying V Zhang, Tudorita Tumbar
Cell proliferation is essential to rapid tissue growth and repair, but can result in replication-associated genome damage. Here, we implicate the transcription factor Gata6 in adult mouse hair follicle regeneration where it controls the renewal of rapidly proliferating epithelial (matrix) progenitors and hence the extent of production of terminally differentiated lineages. We find that Gata6 protects against DNA damage associated with proliferation, thus preventing cell cycle arrest and apoptosis. Furthermore, we show that in vivo Gata6 stimulates EDA-receptor signaling adaptor Edaradd level and NF-κB pathway activation, known to be important for DNA damage repair and stress response in general and for hair follicle growth in particular...
December 1, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27908783/lipid-peroxidation-in-face-of-dna-damage-dna-repair-and-other-cellular-processes
#5
Barbara Tudek, Daria Zdżalik-Bielecka, Agnieszka Tudek, Konrad Kosicki, Anna Fabisiewicz, Elżbieta Speina
Exocyclic adducts to DNA bases are formed as a consequence of exposure to certain environmental carcinogens as well as inflammation and lipid peroxidation (LPO). Complex family of LPO products gives rise to a variety of DNA adducts, which can be grouped in two classes: (i) small etheno-type adducts of strong mutagenic potential, and (ii) bulky, propano-type adducts, which block replication and transcription, and are lethal lesions. Etheno-DNA adducts are removed from the DNA by base excision repair (BER), AlkB and nucleotide incision repair enzymes (NIR), while substituted propano-type lesions by nucleotide excision repair (NER) and homologous recombination (HR)...
November 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27908614/a-critical-discussion-on-diet-genomic-mutations-and-repair-mechanisms-in-colon-carcinogenesis
#6
Juliana Yumi Sakita, Bianca Gasparotto, Sergio Britto Garcia, Sergio Akira Uyemura, Vinicius Kannen
Colon cancer is one of the most common malignancies and its etiology closely tied to dietary habits. Recent epidemiological data shows that colon cancer incidence is shifting to a much younger population. In this regard, some dietary components from a regular human meal might have various DNA-damaging compounds. Given that not every person endure cancer, the colonic malignancy develops throughout decades, and persistent DNA damage promotes cancer when induced at the proper intensity, a critical discussion of possible novel mechanisms by which carcinogens promote these tumors is urgently needed...
November 28, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27908386/genetic-polymorphisms-in-19q13-3-genes-associated-with-alteration-of-repair-capacity-to-bpde-dna-adducts-in-primary-cultured-lymphocytes
#7
Mingyang Xiao, Sha Xiao, Tahar van der Straaten, Ping Xue, Guopei Zhang, Xiao Zheng, Qianye Zhang, Yuan Cai, Cuihong Jin, Jinghua Yang, Shengwen Wu, Guolian Zhu, Xiaobo Lu
Benzo[a]pyrene(B[a]P), and its ultimate metabolite Benzo[a]pyrene 7,8-diol 9,10-epoxide (BPDE), are classic DNA damaging carcinogens. DNA damage in cells caused by BPDE is normally repaired by Nucleotide Excision Repair (NER) and Base Excision Repair (BER). Genetic variations in NER and BER can change individual DNA repair capacity to DNA damage induced by BPDE. In the present study we determined the number of in vitro induced BPDE-DNA adducts in lymphocytes, to reflect individual susceptibility to Polycyclic aromatic hydrocarbons (PAHs)-induced carcinogenesis...
December 2016: Mutation Research
https://www.readbyqxmd.com/read/27908247/knockdown-of-minichromosome-maintenance-proteins-inhibits-foci-forming-of-mediator-of-dna-damage-checkpoint-1-in-response-to-dna-damage-in-human-esophageal-squamous-cell-carcinoma-te-1-cells
#8
Jinzhong Yu, Ruijie Wang, Jinfeng Wu, Zhongqin Dang, Qinsheng Zhang, Bo Li
Esophageal squamous cell carcinoma (ESCC) has a high morbidity in China and its treatment depends greatly on adjuvant chemotherapy. However, DNA damage repair in cancer cells severely affects the outcome of treatment. This study investigated the potential mechanism regarding mediator of DNA-damage checkpoint 1 (MDC1) and minichromosome maintenance proteins (MCMs) during DNA damage in ESCC. Recombinant vectors of MDC1 and MCMs with tags were constructed and transfected into human ESCC cell line TE-1. Immunoprecipitation and mass spectrometry were performed to screen the MCMs interacting with MDC1, and direct interaction was confirmed by glutathione S-transferase (GST) pull-down assay in vitro...
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27908238/thermodynamic-analysis-of-fast-stages-of-specific-lesion-recognition-by-dna-repair-enzymes
#9
REVIEW
N A Kuznetsov, O S Fedorova
The methodology of determination of the thermodynamic parameters of fast stages of recognition and cleavage of DNA substrates is described for the enzymatic processes catalyzed by DNA glycosylases Fpg and hOGG1 and AP endonuclease APE1 during base excision repair (BER) pathway. For this purpose, stopped-flow pre-steady-state kinetic analysis of tryptophan fluorescence intensity changes in proteins and fluorophores in DNA substrates was performed at various temperatures. This approach made it possible to determine the changes of standard Gibbs free energy, enthalpy, and entropy of sequential steps of DNA-substrate binding, as well as activation enthalpy and entropy for the transition complex formation of the catalytic stage...
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27907204/homologous-recombination-and-translesion-dna-synthesis-play-critical-roles-on-tolerating-dna-damage-caused-by-trace-levels-of-hexavalent-chromium
#10
Xu Tian, Keyur Patel, John R Ridpath, Youjun Chen, Yi-Hui Zhou, Dayna Neo, Jean Clement, Minoru Takata, Shunichi Takeda, Julian Sale, Fred A Wright, James A Swenberg, Jun Nakamura
Contamination of potentially carcinogenic hexavalent chromium (Cr(VI)) in the drinking water is a major public health concern worldwide. However, little information is available regarding the biological effects of a nanomoler amount of Cr(VI). Here, we investigated the genotoxic effects of Cr(VI) at nanomoler levels and their repair pathways. We found that DNA damage response analyzed based on differential toxicity of isogenic cells deficient in various DNA repair proteins is observed after a three-day incubation with K2CrO4 in REV1-deficient DT40 cells at 19...
2016: PloS One
https://www.readbyqxmd.com/read/27907095/phenotypic-plasticity-epigenetic-or-genetic-modifications-in-relation-to-the-duration-of-cd-exposure-within-a-microevolution-time-range-in-the-beet-armyworm
#11
Maria Augustyniak, Anna Płachetka-Bożek, Alina Kafel, Agnieszka Babczyńska, Monika Tarnawska, Agnieszka Janiak, Anna Loba, Marta Dziewięcka, Julia Karpeta-Kaczmarek, Agnieszka Zawisza-Raszka
In the case of the pests inhabiting metal polluted or fields where the use of pesticides is common, a natural selection of resistant individuals can occur. This may pose serious problems for humans, agriculture, as well as the economies of many countries. In this study, the hypothesis that multigenerational (120 generations) exposure to cadmium of a beet armyworm population could be a selecting factor toward a more efficient DNA protection was verified. The hemocytes of individuals from two culture strains (control and Cd-exposed) were treated with H2O2 (a DNA-damaging agent) or PBS (reference)...
2016: PloS One
https://www.readbyqxmd.com/read/27906959/pcna-dependent-cleavage-and-degradation-of-sde2-regulates-response-to-replication-stress
#12
Ukhyun Jo, Winson Cai, Jingming Wang, Yoojin Kwon, Alan D D'Andrea, Hyungjin Kim
Maintaining genomic integrity during DNA replication is essential for cellular survival and for preventing tumorigenesis. Proliferating cell nuclear antigen (PCNA) functions as a processivity factor for DNA replication, and posttranslational modification of PCNA plays a key role in coordinating DNA repair against replication-blocking lesions by providing a platform to recruit factors required for DNA repair and cell cycle control. Here, we identify human SDE2 as a new genome surveillance factor regulated by PCNA interaction...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27905394/uvr2-ensures-transgenerational-genome-stability-under-simulated-natural-uv-b-in-arabidopsis-thaliana
#13
Eva-Maria Willing, Thomas Piofczyk, Andreas Albert, J Barbro Winkler, Korbinian Schneeberger, Ales Pecinka
Ground levels of solar UV-B radiation induce DNA damage. Sessile phototrophic organisms such as vascular plants are recurrently exposed to sunlight and require UV-B photoreception, flavonols shielding, direct reversal of pyrimidine dimers and nucleotide excision repair for resistance against UV-B radiation. However, the frequency of UV-B-induced mutations is unknown in plants. Here we quantify the amount and types of mutations in the offspring of Arabidopsis thaliana wild-type and UV-B-hypersensitive mutants exposed to simulated natural UV-B over their entire life cycle...
December 1, 2016: Nature Communications
https://www.readbyqxmd.com/read/27904274/pretreatment-of-ferulic-acid-protects-human-dermal-fibroblasts-against-ultraviolet-a-irradiation
#14
Hyung Jin Hahn, Ki Bbeum Kim, Seunghee Bae, Byung Gon Choi, Sungkwan An, Kyu Joong Ahn, Su Young Kim
BACKGROUND: Approximately 90%~99% of ultraviolet A (UVA) ray reaches the Earth's surface. The deeply penetrating UVA rays induce the formation of reactive oxygen species (ROS), which results in oxidative stress such as photoproducts, senescence, and cell death. Thus, UVA is considered a primary factor that promotes skin aging. OBJECTIVE: Researchers investigated whether pretreatment with ferulic acid protects human dermal fibroblasts (HDFs) against UVA-induced cell damages...
December 2016: Annals of Dermatology
https://www.readbyqxmd.com/read/27903656/yeast-hmo1-linker-histone-reinvented
#15
REVIEW
Arvind Panday, Anne Grove
Eukaryotic genomes are packaged in chromatin. The higher-order organization of nucleosome core particles is controlled by the association of the intervening linker DNA with either the linker histone H1 or high mobility group box (HMGB) proteins. While H1 is thought to stabilize the nucleosome by preventing DNA unwrapping, the DNA bending imposed by HMGB may propagate to the nucleosome to destabilize chromatin. For metazoan H1, chromatin compaction requires its lysine-rich C-terminal domain, a domain that is buried between globular domains in the previously characterized yeast Saccharomyces cerevisiae linker histone Hho1p...
March 2017: Microbiology and Molecular Biology Reviews: MMBR
https://www.readbyqxmd.com/read/27903453/repair-of-8-oxo-7-8-dihydroguanine-in-prokaryotic-and-eukaryotic-cells-properties-and-biological-roles-of-the-fpg-and-ogg1-dna-n-glycosylases
#16
Serge Boiteux, Franck Coste, Bertrand Castaing
Oxidatively damaged DNA results from the attack of sugar and base moieties by reactive oxygen species (ROS), which are formed as byproducts of normal cell metabolism and during exposure to endogenous or exogenous chemical or physical agents. Guanine, having the lowest redox potential, is the DNA base the most susceptible to oxidation, yielding products such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2-6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). In DNA, 8-oxoG was shown to be mutagenic yielding GC to TA transversions upon incorporation of dAMP opposite this lesion by replicative DNA polymerases...
November 26, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27903196/the-impact-of-cobalt-60-source-age-on-biologically-effective-dose-in-high-dose-functional-gamma-knife-radiosurgery
#17
Benjamin H Kann, James B Yu, John M Stahl, James E Bond, Christopher Loiselle, Veronica L Chiang, Ranjit S Bindra, Jason L Gerrard, David J Carlson
OBJECTIVE Functional Gamma Knife radiosurgery (GKRS) procedures have been increasingly used for treating patients with tremor, trigeminal neuralgia (TN), and refractory obsessive-compulsive disorder. Although its rates of toxicity are low, GKRS has been associated with some, if low, risks for serious sequelae, including hemiparesis and even death. Anecdotal reports have suggested that even with a standardized prescription dose, rates of functional GKRS toxicity increase after replacement of an old cobalt-60 source with a new source...
December 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27902925/targeted-inhibition-of-wrn-helicase-replication-stress-and-cancer
#18
REVIEW
Natalie Orlovetskie, Raphael Serruya, Ghada Abboud-Jarrous, Nayef Jarrous
WRN helicase has several roles in genome maintenance, such as replication, base excision repair, recombination, DNA damage response and transcription. These processes are often found upregulated in human cancers, many of which display increased levels of WRN. Therefore, directed inhibition of this RecQ helicase could be beneficial to selective cancer therapy. Inhibition of WRN is feasible by the use of small-molecule inhibitors or application of RNA interference and EGS/RNase P targeting systems. Remarkably, helicase depletion leads to a severe reduction in cell viability due to mitotic catastrophe, which is triggered by replication stress induced by DNA repair failure and fork progression arrest...
November 27, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27901115/p53-coordinates-dna-repair-with-nucleotide-synthesis-by-suppressing-pfkfb3-expression-and-promoting-the-pentose-phosphate-pathway
#19
Derek A Franklin, Yizhou He, Patrick L Leslie, Andrey P Tikunov, Nick Fenger, Jeffrey M Macdonald, Yanping Zhang
Activation of p53 in response to DNA damage is essential for tumor suppression. Although previous studies have emphasized the importance of p53-dependent cell cycle arrest and apoptosis for tumor suppression, recent studies have suggested that other areas of p53 regulation, such as metabolism and DNA damage repair (DDR), are also essential for p53-dependent tumor suppression. However, the intrinsic connections between p53-mediated DDR and metabolic regulation remain incompletely understood. Here, we present data suggesting that p53 promotes nucleotide biosynthesis in response to DNA damage by repressing the expression of the phosphofructokinase-2 (PFK2) isoform 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a rate-limiting enzyme that promotes glycolysis...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899634/homologous-recombination-mediated-by-the-mycobacterial-adnab-helicase-without-end-resection-by-the-adnab-nucleases
#20
Richa Gupta, Mihaela-Carmen Unciuleac, Stewart Shuman, Michael S Glickman
Current models of bacterial homologous recombination (HR) posit that extensive resection of a DNA double-strand break (DSB) by a multisubunit helicase-nuclease machine (e.g. RecBCD, AddAB or AdnAB) generates the requisite 3' single-strand DNA substrate for RecA-mediated strand invasion. AdnAB, the helicase-nuclease implicated in mycobacterial HR, consists of two subunits, AdnA and AdnB, each composed of an N-terminal ATPase domain and a C-terminal nuclease domain. DSB unwinding by AdnAB in vitro is stringently dependent on the ATPase activity of the 'lead' AdnB motor translocating on the 3' ssDNA strand, but not on the putative 'lagging' AdnA ATPase...
November 29, 2016: Nucleic Acids Research
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