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nucleotide excision repair

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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/29148771/an-qm-mm-study-of-the-reaction-catalyzed-by-alkyladenine-dna-glycosylase-examination-of-the-substrate-specificity-of-a-dna-repair-enzyme
#2
Stefan A P Lenz, Stacey D Wetmore
Human alkyladenine DNA glycosylase (AAG) functions as part of the base excision repair pathway to excise structurally diverse oxidized and alkylated DNA purines. Specifically, AAG uses a water molecule activated by a general base and a non-specific active site lined with aromatic residues to cleave the N-glycosidic bond. Despite broad substrate specificity, AAG does not target the natural purines (adenine (A) and guanine (G)). Using the ONIOM(QM:MM) methodology, we provide fundamental atomic level details of AAG bound to DNA-containing a neutral substrate (hypoxanthine (Hx)), a non-substrate (G), or a cationic substrate (7-methylguanine (7MeG)), and probe changes in the reaction pathway that occur when AAG targets different nucleotides...
November 17, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29140456/minimotif-miner-4-a-million-peptide-minimotifs-and-counting
#3
Kenneth F Lyon, Xingyu Cai, Richard J Young, Abdullah-Al Mamun, Sanguthevar Rajasekaran, Martin R Schiller
Minimotif Miner (MnM) is a database and web system for analyzing short functional peptide motifs, termed minimotifs. We present an update to MnM growing the database from ∼300 000 to >1 000 000 minimotif consensus sequences and instances. This growth comes largely from updating data from existing databases and annotation of articles with high-throughput approaches analyzing different types of post-translational modifications. Another update is mapping human proteins and their minimotifs to know human variants from the dbSNP, build 150...
November 11, 2017: Nucleic Acids Research
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
#4
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/29129631/binding-of-calcium-and-target-peptide-to-calmodulin-like-protein-cml19-the-centrin-2-of-arabidopsis-thaliana
#5
Valentina La Verde, Matteo Trande, Mariapina D'Onofrio, Paola Dominici, Alessandra Astegno
Calmodulin-like protein 19 (CML19) is an Arabidopsis centrin that modulates nucleotide excision repair (NER) by binding to RAD4 protein, the Arabidopsis homolog of human Xeroderma pigmentosum complementation group C protein. Although the necessity of CML19 as a part of the RAD4 plant recognition complex for functional NER is known at a cellular level, little is known at a molecular level. Herein, we used a combination of biophysical and biochemical approaches to investigate the structural and ion and target-peptide binding properties of CML19...
November 9, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29128308/oxidative-stress-and-dna-damage-after-cerebral-ischemia-potential-therapeutic-targets-to-preserve-the-genome-and-improve-stroke-recovery
#6
REVIEW
Peiying Li, R Anne Stetler, Rehana K Leak, Yejie Shi, Yan Li, Weifeng Yu, Michael V L Bennett, Jun Chen
The past two decades have witnessed remarkable advances in oxidative stress research, particularly in the context of ischemic brain injury. Oxidative stress in ischemic tissues compromises the integrity of the genome, resulting in DNA lesions, cell death in neurons, glial cells, and vascular cells, and impairments in neurological recovery after stroke. As DNA is particularly vulnerable to oxidative attack, cells have evolved the ability to induce multiple DNA repair mechanisms, including base excision repair (BER), nucleotide excision repair (NER) and non-homogenous endpoint jointing (NHEJ)...
November 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29124689/xeroderma-pigmentosa-group-a-xpa-nucleotide-excision-repair-and-regulation-by-atr-in-response-to-ultraviolet-irradiation
#7
Phillip R Musich, Zhengke Li, Yue Zou
The sensitivity of Xeroderma pigmentosa (XP) patients to sunlight has spurred the discovery and genetic and biochemical analysis of the eight XP gene products (XPA-XPG plus XPV) responsible for this disorder. These studies also have served to elucidate the nucleotide excision repair (NER) process, especially the critical role played by the XPA protein. More recent studies have shown that NER also involves numerous other proteins normally employed in DNA metabolism and cell cycle regulation. Central among these is ataxia telangiectasia and Rad3-related (ATR), a protein kinase involved in intracellular signaling in response to DNA damage, especially DNA damage-induced replicative stresses...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29121049/haplotype-cgc-from-xpd-hogg1-and-itga2-polymorphisms-increases-the-risk-of-nasopharyngeal-carcinoma-in-malaysia
#8
Eng-Zhuan Ban, Munn-Sann Lye, Pei Pei Chong, Yoke-Yeow Yap, Siew Ying Crystale Lim, Hejar Abdul Rahman
BACKGROUND: 8-oxoG, a common DNA lesion resulting from reactive oxygen species (ROS), has been shown to be associated with cancer initiation. hOGG1 DNA glycosylase is the primary enzyme responsible for excision of 8-oxoG through base excision repair (BER). Integrins are members of a family of cell surface receptors that mediate the cell-cell and extracellular matrix (ECM) interactions. Integrins are involved in almost every aspect of carcinogenesis, from cell differentiation, cell proliferation, metastasis to angiogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/29118522/association-of-leukotrichia-in-vitiligo-and-asp148glu-polymorphism-of-apurinic-apyrimidinic-endonuclease-1
#9
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/29113361/a-case-control-study-on-association-of-nucleotide-excision-repair-polymorphisms-and-its-interaction-with-environment-factors-with-the-susceptibility-to-non-melanoma-skin-cancer
#10
Yan-Ling Li, Feng Wei, Yu-Ping Li, Li-Hua Zhang, Yan-Zhi Bai
Aims: To investigate the association of several single nucleotide polymorphisms (SNPs) within nucleotide excision repair (NER) gene and additional gene- gene and gene- smoking interaction with non-melanoma skin cancer (NMSC) risk in a Chinese population. Methods: A total of 1322 participants (939 males, 383 females) were selected, including 660 NMSC patients and 662 control participants. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29112132/autophagy-roles-in-the-modulation-of-dna-repair-pathways
#11
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/29109913/comparative-analysis-of-the-microrna-transcriptome-between-yak-and-cattle-provides-insight-into-high-altitude-adaptation
#12
Jiuqiang Guan, Keren Long, Jideng Ma, Jinwei Zhang, Dafang He, Long Jin, Qianzi Tang, Anan Jiang, Xun Wang, Yaodong Hu, Shilin Tian, Zhi Jiang, Mingzhou Li, Xiaolin Luo
Extensive and in-depth investigations of high-altitude adaptation have been carried out at the level of morphology, anatomy, physiology and genomics, but few investigations focused on the roles of microRNA (miRNA) in high-altitude adaptation. We examined the differences in the miRNA transcriptomes of two representative hypoxia-sensitive tissues (heart and lung) between yak and cattle, two closely related species that live in high and low altitudes, respectively. In this study, we identified a total of 808 mature miRNAs, which corresponded to 715 pre-miRNAs in the two species...
2017: PeerJ
https://www.readbyqxmd.com/read/29109511/ash1l-histone-methyltransferase-regulates-the-handoff-between-damage-recognition-factors-in-global-genome-nucleotide-excision-repair
#13
Chiara Balbo Pogliano, Marco Gatti, Peter Rüthemann, Zuzana Garajovà, Lorenza Penengo, Hanspeter Naegeli
Global-genome nucleotide excision repair (GG-NER) prevents ultraviolet (UV) light-induced skin cancer by removing mutagenic cyclobutane pyrimidine dimers (CPDs). These lesions are formed abundantly on DNA wrapped around histone octamers in nucleosomes, but a specialized damage sensor known as DDB2 ensures that they are accessed by the XPC initiator of GG-NER activity. We report that DDB2 promotes CPD excision by recruiting the histone methyltransferase ASH1L, which methylates lysine 4 of histone H3. In turn, methylated H3 facilitates the docking of the XPC complex to nucleosomal histone octamers...
November 6, 2017: Nature Communications
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
#14
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/29105242/ercc4-variants-identified-in-a-cohort-of-patients-with-segmental-progeroid-syndromes
#15
Takayasu Mori, Matthew J Yousefzadeh, Maryam Faridounnia, Jessica X Chong, Fuki M Hisama, Louanne Hudgins, Gabriela Mercado, Erin A Wade, Amira S Barghouthy, Lin Lee, George M Martin, Deborah A Nickerson, Michael J Bamshad, Laura J Niedernhofer, Junko Oshima
Pathogenic variants in genes, which encode DNA repair and damage response proteins, result in a number of genomic instability syndromes with features of accelerated aging. ERCC4 (XPF) encodes a protein that forms a complex with ERCC1 and is required for the 5' incision during nucleotide excision repair. ERCC4 is also FANCQ, illustrating a critical role in interstrand crosslink repair. Pathogenic variants in this gene cause xeroderma pigmentosum, XFE progeroid syndrome, Cockayne syndrome (CS), and Fanconi anemia...
November 3, 2017: Human Mutation
https://www.readbyqxmd.com/read/29103991/structural-basis-for-the-recognition-and-processing-of-dna-containing-bulky-lesions-by-the-mammalian-nucleotide-excision-repair-system
#16
Alexey N Evdokimov, Alexandra Yu Tsidulko, Alexander V Popov, Yury N Vorobiev, Alexander A Lomzov, Lyudmila S Koroleva, Vladimir N Silnikov, Irina O Petruseva, Olga I Lavrik
Mammalian nucleotide excision repair (NER) eliminates the broadest diversity of bulky lesions from DNA with wide specificity. However, the double incision efficiency for structurally different adducts can vary over several orders of magnitude. Therefore, great attention is drawn to the question of the relationship among structural properties of bulky DNA lesions and the rate of damage elimination. This paper studies the properties of several structurally diverse synthetic (model) DNAs containing bulky modifications...
November 2, 2017: DNA Repair
https://www.readbyqxmd.com/read/29098631/formation-and-repair-of-dna-protein-crosslink-damage
#17
REVIEW
Naeh L Klages-Mundt, Lei Li
DNA is constantly exposed to a wide array of genotoxic agents, generating a variety of forms of DNA damage. DNA-protein crosslinks (DPCs)-the covalent linkage of proteins with a DNA strand-are one of the most deleterious and understudied forms of DNA damage, posing as steric blockades to transcription and replication. If not properly repaired, these lesions can lead to mutations, genomic instability, and cell death. DPCs can be induced endogenously or through environmental carcinogens and chemotherapeutic agents...
October 30, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29082541/mycobacterium-tuberculosis-uvrb-forms-dimers-in-solution-and-interacts-with-uvra-in-the-absence-of-ligands
#18
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
#19
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/29069470/common-tfiih-recruitment-mechanism-in-global-genome-and-transcription-coupled-repair-subpathways
#20
Masahiko Okuda, Yuka Nakazawa, Chaowan Guo, Tomoo Ogi, Yoshifumi Nishimura
Nucleotide excision repair is initiated by two different damage recognition subpathways, global genome repair (GGR) and transcription-coupled repair (TCR). In GGR, XPC detects DNA lesions and recruits TFIIH via interaction with the pleckstrin homology (PH) domain of TFIIH subunit p62. In TCR, an elongating form of RNA Polymerase II detects a lesion on the transcribed strand and recruits TFIIH by an unknown mechanism. Here, we found that the TCR initiation factor UVSSA forms a stable complex with the PH domain of p62 via a short acidic string in the central region of UVSSA, and determined the complex structure by NMR...
October 24, 2017: Nucleic Acids Research
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