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https://www.readbyqxmd.com/read/27908783/lipid-peroxidation-in-face-of-dna-damage-dna-repair-and-other-cellular-processes
#1
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/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
#2
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/27864884/mfd-protein-and-transcription-repair-coupling-in-e-coli
#3
Christopher P Selby
In 1989, transcription-repair coupling (TRC) was first described in Escherichia coli, as the transcription-dependent, preferential nucleotide excision repair (NER) of UV photoproducts located in the template DNA strand. This finding led to pioneering biochemical studies of TRC in the laboratory of Professor Aziz Sancar, where, at the time, major contributions were being made toward understanding the roles of the UvrA, UvrB and UvrC proteins in NER. When the repair studies were extended to TRC, template but not coding strand lesions were found to block RNA polymerase (RNAP) in vitro, and unexpectedly, the blocked RNAP inhibited NER...
November 19, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27861965/impact-of-the-circadian-clock-on-uv-induced-dna-damage-response-and-photocarcinogenesis
#4
Panshak Dakup, Shobhan Gaddameedhi
The skin is in constant exposure to various external environmental stressors, including solar ultraviolet (UV) radiation. Various wavelengths of UV light are absorbed by the DNA and other molecules in the skin to cause DNA damage and induce oxidative stress. The exposure to excessive ultraviolet (UV) radiation and/or accumulation of damage over time can lead to photocarcinogenesis and photoaging. The nucleotide excision repair (NER) system is the sole mechanism for removing UV photoproduct damage from DNA, and genetic disruption of this repair pathway leads to the photosensitive disorder xeroderma pigmentosum (XP)...
November 12, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27859304/from-mfd-to-trcf-and-back-again-a-perspective-on-bacterial-transcription-coupled-nucleotide-excision-repair
#5
Alexandra M Deaconescu, Margaret M Suhanovsky
Photochemical and other reactions on DNA cause damage and corrupt genetic information. To counteract this damage, organisms have evolved intricate repair mechanisms that often crosstalk with other DNA-based processes, such as transcription. Intriguing observations in the late 1980s and early 1990s led to the discovery of transcription-coupled repair (TCR), a subpathway of nucleotide excision repair (NER). TCR, found in all domains of life prioritizes for repair lesions located in the transcribed DNA strand, directly read by RNA polymerase...
November 12, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27858292/cisplatin-toxicity-in-dorsal-root-ganglion-neurons-is-relieved-by-meclizine-via-diminution-of-mitochondrial-compromise-and-improved-clearance-of-dna-damage
#6
Murat F Gorgun, Ming Zhuo, Ella W Englander
Chemotherapy-induced neurotoxicity of peripheral nervous system (PNS) hinders efficacy of cancer treatments. Mechanisms initiating PNS injury by anticancer drugs are incompletely understood delaying development of effective management strategies. To understand events triggered in PNS by cancer drugs, we exposed dorsal root ganglion (DRG) neurons to cisplatin, a drug from platinum-based class of chemotherapeutics frequently implicated in peripheral neuropathies. While cisplatin enters cancer cells and forms cisplatin/DNA crosslinks that block cell proliferation, circulating cisplatin can also reach the PNS and produce crosslinks that impede critical DNA transactions in postmitotic neurons...
November 17, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27827925/transcriptional-and-posttranslational-regulation-of-nucleotide-excision-repair-the-guardian-of-the-genome-against-ultraviolet-radiation
#7
REVIEW
Jeong-Min Park, Tae-Hong Kang
Ultraviolet (UV) radiation from sunlight represents a constant threat to genome stability by generating modified DNA bases such as cyclobutane pyrimidine dimers (CPD) and pyrimidine-pyrimidone (6-4) photoproducts (6-4PP). If unrepaired, these lesions can have deleterious effects, including skin cancer. Mammalian cells are able to neutralize UV-induced photolesions through nucleotide excision repair (NER). The NER pathway has multiple components including seven xeroderma pigmentosum (XP) proteins (XPA to XPG) and numerous auxiliary factors, including ataxia telangiectasia and Rad3-related (ATR) protein kinase and RCC1 like domain (RLD) and homologous to the E6-AP carboxyl terminus (HECT) domain containing E3 ubiquitin protein ligase 2 (HERC2)...
November 4, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27818219/removal-of-oxidatively-generated-dna-damage-by-overlapping-repair-pathways
#8
REVIEW
Vladimir Shafirovich, Nicholas E Geacintov
It is generally believed that the mammalian nucleotide excision repair pathway removes DNA helix-distorting bulky DNA lesions, while small non-bulky lesions are repaired by base excision repair (BER). However, recent work demonstrates that the oxidativly generated guanine oxidation products, spiroimininodihydantoin (Sp), 5-guanidinohydantoin (Gh), and certain intrastrand cross-linked lesions, are good substrates of NER and BER pathways that compete with one another in human cell extracts. The oxidation of guanine by peroxynitrite is known to generate 5-guanidino-4-nitroimidazole (NIm) which is structurally similar to Gh, except that the 4-nitro group in NIm is replaced by a keto group in Gh...
November 4, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27803034/comparison-of-the-dna-damage-response-in-beas-2b-and-a549-cells-exposed-to-titanium-dioxide-nanoparticles
#9
M Biola-Clier, D Beal, S Caillat, S Libert, L Armand, N Herlin-Boime, S Sauvaigo, T Douki, M Carriere
For some decades production of titanium dioxide nanoparticle (TiO2-NP) has been increasing at a considerable rate; concerns as to the toxicity of these particles upon inhalation have been raised. Indeed, TiO2-NPs have been shown to induce significant genotoxicity and to adversely affect both major DNA repair mechanisms: base excision repair (BER) and nucleotide excision repair (NER). The aims of the present study were to (i) compare the genotoxicity of TiO2-NPs and their impact on DNA repair processes on A549 alveolar carcinoma and BEAS-2B normal bronchial lung cell lines and (ii) delve deeper into the mechanisms leading to these effects...
November 1, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27802208/mms19-as-a-potential-predictive-marker-of-adjuvant-chemotherapy-benefit-in-resected-non-small-cell-lung-cancer
#10
Julien Adam, Tony Sourisseau, Ken A Olaussen, Angélique Robin, Chang Q Zhu, Alexandre Templier, Alexandre Civet, Philippe Girard, Vladimir Lazar, Pierre Validire, Ming S Tsao, Jean-Charles Soria, Benjamin Besse
BACKGROUND: Resectable non-small cell lung cancer (NSCLC) treatment options most often consist of surgical resection along with adjuvant chemotherapy (ACT). The benefit of ACT however is modest and is accompanied by important side effects. OBJECTIVE: One central quest in the field is therefore the identification of a predictive marker of the response to ACT. METHODS: We applied an unbiased approach based on high content analysis of expression data generated from a discovery patient cohort...
September 26, 2016: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27794614/role-of-dna-repair-factor-xpc-in-response-to-replication-stress-revealed-by-dna-fragile-site-affinity-chromatography-and-quantitative-proteomics
#11
Lucie Beresova, Eva Vesela, Ivo Chamrád, Jiri Voller, Masayuki Yamada, Tomas Furst, Rene Lenobel, Katarina Chroma, Jan Gursky, Katerina Krizova, Martin Mistrik, Jiri Bartek
Replication stress (RS) fuels genomic instability and cancer development and may contribute to ageing, raising the need to identify factors involved in cellular responses to such stress. Here, we present a strategy for identification of factors affecting the maintenance of common fragile sites (CFSs), genomic loci that are particularly sensitive to RS and suffer from increased breakage and rearrangements in tumors. A DNA probe designed to match the high flexibility island sequence typical for the commonly expressed CFS (FRA16D) was used as specific DNA affinity bait...
October 30, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27793847/dna-repair-capacity-in-multiple-pathways-predicts-chemoresistance-in-glioblastoma-multiforme
#12
Zachary D Nagel, Gaspar J Kitange, Shiv K Gupta, Brian A Joughin, Isaac A Chaim, Patrizia Mazzucato, Douglas A Lauffenburger, Jann N Sarkaria, Leona D Samson
Cancer cells can resist the effects of DNA-damaging therapeutic agents via utilization of DNA repair pathways, suggesting that DNA repair capacity (DRC) measurements in cancer cells could be used to identify patients most likely to respond to treatment. However, the limitations of available technologies have so far precluded adoption of this approach in the clinic. We recently developed fluorescence-based multiplexed host cell reactivation (FM-HCR) assays to measure DRC in multiple pathways. Here we apply a mathematical model that uses DRC in multiple pathways to predict cellular resistance to killing by DNA-damaging agents...
October 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/27773933/targeting-transcription-coupled-nucleotide-excision-repair-overcomes-resistance-in-chronic-lymphocytic-leukemia
#13
G Lohmann, E Vasyutina, J Bloehdorn, N Reinart, J I Schneider, V Babu, G Knittel, G Crispatzu, P Mayer, C Prinz, J K Muenzner, B Biersack, D G Efremov, L Chessa, C D Herling, S Stilgenbauer, M Hallek, R Schobert, H C Reinhardt, B Schumacher, M Herling
Treatment resistance becomes a challenge at some point in the course of most patients with chronic lymphocytic leukemia (CLL). This applies to fludarabine-based regimens, and is also an increasing concern in the era of more targeted therapies. As cells with low-replicative activity rely on repair that triggers checkpoint-independent noncanonical pathways, we reasoned that targeting the nucleotide excision repair (NER) reaction addresses a vulnerability of CLL and might even synergize with fludarabine, which blocks the NER gap-filling step...
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27768589/nucleotide-excision-repair-pathway-gene-polymorphisms-are-linked-to-breast-cancer-risk-in-a-chinese-population
#14
Bang-Shun He, Tao Xu, Yu-Qin Pan, Han-Jin Wang, William C Cho, Kang Lin, Hui-Ling Sun, Tian-Yi Gao, Shu-Kui Wang
Polymorphisms in nucleotide excision repair (NER) pathway genes are associated with the risk of breast cancer, but the relevance of these associations appeared to vary according to the ethnicity of the subjects. To systemically evaluate the potential associations between NER polymorphisms and breast cancer risk in a Chinese population, we carried out a case-control study on 450 breast cancer patients and 430 healthy controls. Sequenom MassARRAY was used for genotyping, and immunohistochemistry was performed to detect estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression in tumor tissue...
October 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27738139/the-multifaceted-influence-of-histone-deacetylases-on-dna-damage-signalling-and-dna-repair
#15
Wynand Paul Roos, Andrea Krumm
Histone/protein deacetylases play multiple roles in regulating gene expression and protein activation and stability. Their deregulation during cancer initiation and progression cause resistance to therapy. Here, we review the role of histone deacetylases (HDACs) and the NAD(+) dependent sirtuins (SIRTs) in the DNA damage response (DDR). These lysine deacetylases contribute to DNA repair by base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), non-homologous end joining (NHEJ), homologous recombination (HR) and interstrand crosslink (ICL) repair...
October 13, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27737893/emerging-roles-for-histone-modifications-in-dna-excision-repair
#16
Peng Mao, John J Wyrick
DNA repair is critical to maintain genome stability. In eukaryotic cells, DNA repair is complicated by the packaging of the DNA 'substrate' into chromatin. DNA repair pathways utilize different mechanisms to overcome the barrier presented by chromatin to efficiently locate and remove DNA lesions in the genome. DNA excision repair pathways are responsible for repairing a majority of DNA lesions arising in the genome. Excision repair pathways include nucleotide excision repair (NER) and base excision repair (BER), which repair bulky and non-bulky DNA lesions, respectively...
October 12, 2016: FEMS Yeast Research
https://www.readbyqxmd.com/read/27736029/a-platinum-iv-anticancer-prodrug-targeting-nucleotide-excision-repair-to-overcome-cisplatin-resistance
#17
Zhigang Wang, Zoufeng Xu, Guangyu Zhu
DNA damage response plays a key role not only in maintaining genome integrity but also in mediating the antitumor efficacy of DNA-damaging antineoplastic drugs. Herein, we report the rational design and evaluation of a Pt(IV) anticancer prodrug inhibiting nucleotide excision repair (NER), one of the most pivotal processes after the formation of cisplatin-induced DNA damage that deactivates the drug and leads to drug resistance in the clinic. This dual-action prodrug enters cells efficiently and causes DNA damage while simultaneously inhibiting NER to promote apoptotic response...
October 13, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27711223/the-bacterial-mfd-protein-prevents-dna-damage-induced-by-the-host-nitrogen-immune-response-in-a-ner-independent-but-recbc-dependent-pathway
#18
Claire Darrigo, Elisabeth Guillemet, Rozenn Dervyn, Nalini Ramarao
Production of reactive nitrogen species is an important component of the host immune defence against bacteria. Here, we show that the bacterial protein Mfd (Mutation frequency decline), a highly conserved and ubiquitous bacterial protein involved in DNA repair, confers bacterial resistance to the eukaryotic nitrogen response produced by macrophage cells and during mice infection. In addition, we show that RecBC is also necessary to survive this stress. The inactivation of recBC and mfd genes is epistatic showing that Mfd follows the RecBC repair pathway to protect the bacteria against the genotoxic effect of nitrite...
2016: PloS One
https://www.readbyqxmd.com/read/27696486/nucleotide-excision-repair-finely-tuned-molecular-orchestra-of-early-pre-incision-events
#19
Qianzheng Zhu, Altaf A Wani
Nucleotide excision repair (NER) eliminates a broad variety of helix-distorting DNA lesions that can otherwise cause genomic instability. NER comprises two distinct sub-pathways: global genomic NER (GG-NER) operating throughout the genome, and transcription-coupled NER (TC-NER) preferentially removing DNA lesions from transcribing DNA strands of transcriptionally active genes. Several NER factors undergo post-translational modifications, including ubiquitination, occurring swiftly and reversibly at DNA lesion sites...
October 1, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27693244/impact-of-dna-repair-on-the-dose-response-of-colorectal-cancer-formation-induced-by-dietary-carcinogens
#20
Jörg Fahrer, Bernd Kaina
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, which is causally linked to dietary habits, notably the intake of processed and red meat. Processed and red meat contain dietary carcinogens, including heterocyclic aromatic amines (HCAs) and N-nitroso compounds (NOC). NOC are agents that induce various N-methylated DNA adducts and O(6)-methylguanine (O(6)-MeG), which are removed by base excision repair (BER) and O(6)-methylguanine-DNA methyltransferase (MGMT), respectively. HCAs such as the highly mutagenic 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) cause bulky DNA adducts, which are removed from DNA by nucleotide excision repair (NER)...
October 6, 2016: Food and Chemical Toxicology
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