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https://www.readbyqxmd.com/read/29149600/repair-of-uv-induced-dna-damage-independent-of-nucleotide-excision-repair-is-masked-by-mutyh
#1
Abdelghani Mazouzi, Federica Battistini, Sarah C Moser, Joana Ferreira da Silva, Marc Wiedner, Michel Owusu, Charles-Hugues Lardeau, Anna Ringler, Beatrix Weil, Jürgen Neesen, Modesto Orozco, Stefan Kubicek, Joanna I Loizou
DNA lesions caused by UV damage are thought to be repaired solely by the nucleotide excision repair (NER) pathway in human cells. Patients carrying mutations within genes functioning in this pathway display a range of pathologies, including an increased susceptibility to cancer, premature aging, and neurological defects. There are currently no curative therapies available. Here we performed a high-throughput chemical screen for agents that could alleviate the cellular sensitivity of NER-deficient cells to UV-induced DNA damage...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29134637/ercc4-regulatory-variant-predict-grade-3-or-4-toxicities-in-patients-with-advanced-non-small-cell-lung-cancer-treated-by-platinum-based-therapy
#2
Ruoxin Zhang, Ming Jia, Yuan Xu, Danwen Qian, Mengyun Wang, Meiling Zhu, Menghong Sun, Jianhua Chang, Qingyi Wei
Platinum-based chemotherapy (PBC) in combination with the 3(rd) generation drugs is the first-line treatment for patients with advanced non-small cell lung cancer (NSCLC); however, the efficacy is severely hampered by grade 3-4 toxicities. Nucleotide excision repair (NER) pathway is the main mechanism of removing platinum-induced DNA adducts, contributing to the toxicity and outcome of PBC. We analyzed data from 710 Chinese NSCLC patients treated with PBC and assessed the associations of 25 potentially functional single nucleotide polymorphisms (SNPs) in eight NER core genes with overall, gastrointestinal and hematologic toxicities...
November 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29114686/modulation-of-xpc-peptide-on-binding-tb-3-to-euplotes-octocarinatus-centrin
#3
Enxian Shi, Wenlong Zhang, Yaqin Zhao, Binsheng Yang
Centrins are Ca(2+)-binding proteins found throughout eukaryotic organisms. Xeroderma pigmentosum group C protein (XPC), a dominant component of the nuclear excision repair (NER) pathway, is a critical target protein of centrins. A 22-residue peptide (K842-R863) from XPC was used to investigate the effect of metal ions (Ca(2+) and Tb(3+)) on the peptide binding of Euplotes octocarinatus centrin (EoCen) by isothermal titration calorimetry (ITC) and fluorescence spectroscopy. ITC and tryptophan spectrofluorimetric titrations revealed that metal ions (Ca(2+) and Tb(3+)) could enhance the affinity between EoCen and the XPC peptide, and the enhanced effects were closely related to the ion potential of metal ions...
November 8, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29112132/autophagy-roles-in-the-modulation-of-dna-repair-pathways
#4
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/29082541/mycobacterium-tuberculosis-uvrb-forms-dimers-in-solution-and-interacts-with-uvra-in-the-absence-of-ligands
#5
Samarpita Lahiri, Menico Rizzi, Franca Rossi, Riccardo Miggiano
During its life cycle Mycobacterium tuberculosis (MTB) must face a variety of environmental and endogenous physical and chemical stresses that could produce genotoxic damage. However, MTB possesses efficient systems to counteract the harmful effects of DNA-damaging assaults. The Nucleotide Excision Repair (NER) is a highly conserved multi-enzymatic cascade that is initiated by the concerted action of three core proteins, i.e. UvrA, UvrB and UvrC. Although the functional roles of these enzymes are well characterized, the intra-pathway coordination of the NER components and the dynamics of their association is still a matter of debate...
October 30, 2017: Proteins
https://www.readbyqxmd.com/read/29078353/mutagenic-cost-of-ribonucleotides-in-bacterial-dna
#6
Jeremy W Schroeder, Justin R Randall, William G Hirst, Michael E O'Donnell, Lyle A Simmons
Replicative DNA polymerases misincorporate ribonucleoside triphosphates (rNTPs) into DNA approximately once every 2,000 base pairs synthesized. Ribonucleotide excision repair (RER) removes ribonucleoside monophosphates (rNMPs) from genomic DNA, replacing the error with the appropriate deoxyribonucleoside triphosphate (dNTP). Ribonucleotides represent a major threat to genome integrity with the potential to cause strand breaks. Furthermore, it has been shown in the bacterium Bacillus subtilis that loss of RER increases spontaneous mutagenesis...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29045565/cigarette-sidestream-smoke-delays-nucleotide-excision-repair-inhibited-accumulation-of-repair-proteins-at-dna-lesions
#7
Guang Yang, Yuko Ibuki
Cigarette sidestream smoke (CSS) contains many carcinogens that induce DNA damage. DNA damage plays an important role in the initiation of cancer and several diseases, and repair is the major defense mechanism; however, the relationship between CSS and the repair of DNA damage remains unclear. We herein investigated whether CSS influences nucleotide excision repair (NER) in vivo and in vitro. HR-1 hairless mouse skin treated with CSS was exposed to UVB, as a result of which pyrimidine dimers (cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs)) were formed and repaired via the NER pathway...
October 13, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28981631/uv-radiation-induced-sumoylation-of-ddb2-regulates-nucleotide-excision-repair
#8
Chunhua Han, Ran Zhao, John Kroger, Jinshan He, Gulzar Wani, Qi-En Wang, Altaf A Wani
Subunit 2 of DNA damage-binding protein complex (DDB2) is an early sensor of nucleotide excision repair (NER) pathway for eliminating DNA damage induced by UV radiation (UVR) and cisplatin treatments of mammalian cells. DDB2 is modified by ubiquitin and poly(ADP-ribose) (PAR) in response to UVR, and these modifications play a crucial role in regulating NER. Here, using immuno-analysis of irradiated cell extracts, we have identified multiple post-irradiation modifications of DDB2 protein. Interestingly, although the DNA lesions induced by both UVR and cisplatin are corrected by NER, only the UV irradiation, but not the cisplatin treatment, induces any discernable DDB2 modifications...
October 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28943968/high-excision-repair-cross-complementation-group-1-expression-is-associated-with-favorable-prognostic-factors-in-breast-cancer
#9
Dong Hyun Kim, Hyunjoo Lee, Dong-Hoon Kim, Seoung Wan Chae, Jin Hee Sohn, Kyungeun Kim, Sung-Im Do
Distortion of DNA can inhibit transcription and replication, resulting in cell death. The nucleotide excision repair (NER) pathway recognizes and repairs DNA adducts. Excision repair cross-complementation group 1 (ERCC1) is a nuclease that serves a vital role in the NER pathway. Few studies have investigated ERCC1 expression in breast cancer. The aim of the present study was to analyze the association between clinicopathological features and ERCC1 expression in breast cancer. ERCC1 expression was studied in 224 invasive ductal carcinomas by immunohistochemical staining...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28936718/identification-of-candidate-genes-for-generalized-tonic-clonic-seizures-in-noda-epileptic-rat
#10
Takashi Kuramoto, Birger Voigt, Satoshi Nakanishi, Kazuhiro Kitada, Tadashi Nakamura, Kaori Wakamatsu, Minako Yoshihara, Mikita Suyama, Risa Uemura, Miyuu Tanaka, Mitsuru Kuwamura, Saki Shimizu, Yukihiro Ohno, Masashi Sasa, Tadao Serikawa
The Noda epileptic rat (NER) exhibits generalized tonic-clonic seizures (GTCS). A genetic linkage analysis identified two GTCS-associated loci, Ner1 on Chr 1 and Ner3 on Chr 5. The wild-type Ner1 and Ner3 alleles suppressed GTCS when combined in double-locus congenic lines, but not when present in single-locus congenic lines. Global expression analysis revealed that cholecystokinin B receptor (Cckbr) and suppressor of tumorigenicity 5 (St5), which map within Ner1, and PHD finger protein 24 (Phf24), which maps within Ner3, were significantly downregulated in NER...
September 21, 2017: Behavior Genetics
https://www.readbyqxmd.com/read/28934497/systematic-analysis-of-dna-crosslink-repair-pathways-during-development-and-aging-in-caenorhabditis-elegans
#11
David M Wilson, Matthias Rieckher, Ashley B Williams, Björn Schumacher
DNA interstrand crosslinks (ICLs) are generated by endogenous sources and chemotherapeutics, and pose a threat to genome stability and cell survival. Using Caenorhabditis elegans mutants, we identify DNA repair factors that protect against the genotoxicity of ICLs generated by trioxsalen/ultraviolet A (TMP/UVA) during development and aging. Mutations in nucleotide excision repair (NER) components (e.g. XPA-1 and XPF-1) imparted extreme sensitivity to TMP/UVA relative to wild-type animals, manifested as developmental arrest, defects in adult tissue morphology and functionality, and shortened lifespan...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28933851/design-and-structure-guided-development-of-novel-inhibitors-of-the-xeroderma-pigmentosum-group-a-xpa-protein-dna-interaction
#12
Navnath S Gavande, Pamela VanderVere-Carozza, Akaash K Mishra, Tyler L Vernon, Katherine S Pawelczak, John J Turchi
XPA is a unique and essential protein required for the nucleotide excision DNA repair pathway and represents a therapeutic target in oncology. Herein, we are the first to develop novel inhibitors of the XPA-DNA interaction through structure-guided drug design efforts. Ester derivatives of the compounds 1 (X80), 22, and 24 displayed excellent inhibitory activity (IC50 of 0.82 ± 0.18 μM and 1.3 ± 0.22 μM, respectively) but poor solubility. We have synthesized novel amide derivatives that retain potency and have much improved solubility...
October 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28924235/single-nucleotide-polymorphisms-of-nucleotide-excision-repair-pathway-are-significantly-associated-with-outcomes-of-platinum-based-chemotherapy-in-lung-cancer
#13
Xiao Song, Shiming Wang, Xuan Hong, Xiaoying Li, Xueying Zhao, Cong Huai, Hongyan Chen, Zhiqiang Gao, Ji Qian, Jiucun Wang, Baohui Han, Chunxue Bai, Qiang Li, Junjie Wu, Daru Lu
Nucleotide excision repair (NER) pathway plays critical roles in repairing DNA disorders caused by platinum. To comprehensively understand the association between variants of NER and clinical outcomes of platinum-based chemotherapy, 173 SNPs in 27 genes were selected to evaluate association with toxicities and efficiency in 1004 patients with advanced non-small cell lung cancer. The results showed that consecutive significant signals were observed in XPA, RPA1, POLD1, POLD3. Further subgroup analysis showed that GTF2H4 presented consecutive significant signals in clinical benefit among adenocarcimoma...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28854356/multilayered-reprogramming-in-response-to-persistent-dna-damage-in-c-%C3%A2-elegans
#14
Diletta Edifizi, Hendrik Nolte, Vipin Babu, Laia Castells-Roca, Michael M Mueller, Susanne Brodesser, Marcus Krüger, Björn Schumacher
DNA damage causally contributes to aging and age-related diseases. Mutations in nucleotide excision repair (NER) genes cause highly complex congenital syndromes characterized by growth retardation, cancer susceptibility, and accelerated aging in humans. Orthologous mutations in Caenorhabditis elegans lead to growth delay, genome instability, and accelerated functional decline, thus allowing investigation of the consequences of persistent DNA damage during development and aging in a simple metazoan model. Here, we conducted proteome, lipidome, and phosphoproteome analysis of NER-deficient animals in response to UV treatment to gain comprehensive insights into the full range of physiological adaptations to unrepaired DNA damage...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28854354/pcaf-gcn5-mediated-acetylation-of-rpa1-promotes-nucleotide-excision-repair
#15
Meimei Zhao, Rui Geng, Xiang Guo, Ruoshi Yuan, Xiao Zhou, Yanyan Zhong, Yanfei Huo, Mei Zhou, Qinjian Shen, Yinglu Li, Weiguo Zhu, Jiadong Wang
The RPA complex can integrate multiple stress signals into diverse responses by activating distinct DNA repair pathways. However, it remains unclear how RPA1 elects to activate a specific repair pathway during different types of DNA damage. Here, we report that PCAF/GCN5-mediated K163 acetylation of RPA1 is crucial for nucleotide excision repair (NER) but is dispensable for other DNA repair pathways. Mechanistically, we demonstrate that the acetylation of RPA1 is critical for the steady accumulation of XPA at damaged DNA sites and preferentially activates the NER pathway...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28801227/estrogen-directly-stimulates-lhb-expression-at-the-pituitary-level-during-puberty-in-female-zebrafish
#16
Gaofei Li, Haipei Tang, Yu Chen, Yike Yin, Satoshi Ogawa, Meifeng Liu, Yin Guo, Xin Qi, Yun Liu, Ishwar S Parhar, Xiaochun Liu, Haoran Lin
The LHb expression is up-regulated during puberty in female zebrafish. However, the molecular mechanism underlying how LHb expression is regulated during puberty remains largely unknown. In this study, we found that the mRNA expression levels of lhb, fshb and cyp19a1b were up-regulated along with the puberty onset in zebrafish. Among the three nuclear estrogen receptors (nERs), the esr2b is the only type whose expression is significantly up-regulated during puberty onset in the pituitary. However, in situ hybridization results revealed that lhb mRNA was colocalized with esr1 and esr2a but not esr2b...
August 8, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28796034/the-association-between-xpg-polymorphisms-and-cancer-susceptibility-evidence-from-observational-studies
#17
REVIEW
Cuihong Han, Xiaoyi Huang, Ruixi Hua, Shujie Song, Lihua Lyu, Na Ta, Jinhong Zhu, Peixi Zhang
BACKGROUND: Exposure to environmental carcinogens can cause damages to DNA. If not properly repaired, the DNA damages may increase the risk of carcinogenesis. Xeroderma pigmentosum group G (XPG) gene is an essential gene in the nucleotide excision repair (NER) pathway. The association between XPG polymorphisms and cancer susceptibility has been the focus of attention in the molecular epidemiology of cancer. However, the conclusions have been divergent. Therefore, we conducted a comprehensive meta-analysis to precisely evaluate the association of 3 frequently investigated XPG polymorphisms (rs751402, rs873601, and rs2296147) with cancer risk...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28783563/stimulation-of-rna-polymerase-ii-ubiquitination-and-degradation-by-yeast-mrna-3-end-processing-factors-is-a-conserved-dna-damage-response-in-eukaryotes
#18
Jason N Kuehner, James W Kaufman, Claire Moore
The quality and retrieval of genetic information is imperative to the survival and reproduction of all living cells. Ultraviolet (UV) light induces lesions that obstruct DNA access during transcription, replication, and repair. Failure to remove UV-induced lesions can abrogate gene expression and cell division, resulting in permanent DNA mutations. To defend against UV damage, cells utilize transcription-coupled nucleotide excision repair (TC-NER) to quickly target lesions within active genes. In cases of long-term genotoxic stress, a slower alternative pathway promotes degradation of RNA Polymerase II (Pol II) to allow for global genomic nucleotide excision repair (GG-NER)...
September 2017: DNA Repair
https://www.readbyqxmd.com/read/28759018/toxicity-and-repair-of-dna-adducts-produced-by-the-natural-product-yatakemycin
#19
Elwood A Mullins, Rongxin Shi, Brandt F Eichman
Yatakemycin (YTM) is an extraordinarily toxic DNA alkylating agent with potent antimicrobial and antitumor properties and is the most recent addition to the CC-1065 and duocarmycin family of natural products. Though bulky DNA lesions the size of those produced by YTM are normally removed from the genome by the nucleotide-excision repair (NER) pathway, YTM adducts are also a substrate for the bacterial DNA glycosylases AlkD and YtkR2, unexpectedly implicating base-excision repair (BER) in their elimination. The reason for the extreme toxicity of these lesions and the molecular basis for the way they are eliminated by BER have been unclear...
September 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28752642/genome-wide-map-of-apn1-binding-sites-under-oxidative-stress-in-saccharomyces-cerevisiae
#20
Lydia P Morris, Andrew B Conley, Natalya Degtyareva, I King Jordan, Paul W Doetsch
The DNA is cells is continuously exposed to reactive oxygen species resulting in toxic and mutagenic DNA damage. Although the repair of oxidative DNA damage occurs primarily through the base excision repair (BER) pathway, the nucleotide excision repair (NER) pathway processes some of the same lesions. In addition, damage tolerance mechanisms, such as recombination and translesion synthesis, enable cells to tolerate oxidative DNA damage, especially when BER and NER capacities are exceeded. Thus, disruption of BER alone or disruption of BER and NER in Saccharomyces cerevisiae leads to increased mutations as well as large-scale genomic rearrangements...
November 2017: Yeast
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