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nucleotide excision repair

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https://www.readbyqxmd.com/read/28088761/amplification-of-unscheduled-dna-synthesis-signal-enables-fluorescence-based-single-cell-quantification-of-transcription-coupled-nucleotide-excision-repair
#1
Franziska Wienholz, Wim Vermeulen, Jurgen A Marteijn
Nucleotide excision repair (NER) comprises two damage recognition pathways: global genome NER (GG-NER) and transcription-coupled NER (TC-NER), which remove a wide variety of helix-distorting lesions including UV-induced damage. During NER, a short stretch of single-stranded DNA containing damage is excised and the resulting gap is filled by DNA synthesis in a process called unscheduled DNA synthesis (UDS). UDS is measured by quantifying the incorporation of nucleotide analogues into repair patches to provide a measure of NER activity...
January 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28076683/modulation-of-cytotoxicity-by-transcription-coupled-nucleotide-excision-repair-is-independent-of-the-requirement-for-bioactivation-of-acylfulvene
#2
Claudia Otto, Graciela Spivak, Claudia Marie Nathalie Aloisi, Mirco Menigatti, Hanspeter Nägeli, Philip C Hanawalt, Marina Tanasova, Shana J Sturla
Bioactivation as well as DNA repair affect the susceptibility of cancer cells to the action of DNA-alkylating chemotherapeutic drugs. However, information is limited with regard to the relative contributions of these processes to the biological outcome of metabolically activated DNA alkylating agents. We evaluated the influence of cellular bioactivation capacity and DNA repair on cytotoxicity of the DNA alkylating agent, acylfulvene (AF). We compared cytotoxicity and RNA synthesis inhibition by AF and its synthetic activated analog iso-M0 in a panel of fibroblast cell lines with deficiencies in transcription-coupled (TC-NER) or global genome nucleotide excision repair (GG-NER)...
January 11, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28074905/mir-488-inhibits-proliferation-and-cisplatin-sensibility-in-non-small-cell-lung-cancer-nsclc-cells-by-activating-the-eif3a-mediated-ner-signaling-pathway
#3
Chao Fang, Yi-Xin Chen, Na-Yiyuan Wu, Ji-Ye Yin, Xiang-Ping Li, Hsuan-Shun Huang, Wei Zhang, Hong-Hao Zhou, Zhao-Qian Liu
Our previous studied indicated that eukaryotic translation initiation factor 3a (eIF3a) increases the sensitive of platinum-based chemotherapy in lung cancer. MiRNAs play an important role in lung carcinogenesis and drug response. In this study, we aimed to identify potential endogenous miRNAs that inhibit eIF3a expression and determine their influence of this inhibition on cisplatin resistance. Using bioinformatics analysis prediction and confirmation with dual-luciferase reporter assays, we found that miRNA-488 inhibited eIF3a expression by directly binding to the 3'UTR of eIF3a...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28074418/identification-of-low-molecular-weight-vitellogenin-1-vg1-like-proteins-as-nucleotide-excision-repair-ner-factors-in-developing-zebrafish-danio-rerio-using-a-transcription-based-dna-repair-assay
#4
Yung-Chi Shen, Todd Hsu, Li-Bin Ling, Wen-Chian You, Chia-Wei Liu
Nucleotide excision repair (NER) removes helix-distorting DNA lesions such as UV-induced pyrimidine dimers and cisplatin-induced strand crosslinking. Our earlier studies have identified low-molecular-weight proteins homologous to the 150-kDa vitellogenin 1 (Vg1) as UV-damaged DNA-binding factors expressed in developing zebrafish (Danio rerio). This present study explored if Vg1-like proteins also participated in NER in zebrafish. Immunoblot analysis of affinity-captured 12 h post-fertilization (hpf) zebrafish extract proteins showed a transient binding of a 30-kDa Vg1-like polypeptide to UV-damaged DNA...
January 10, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28074003/dna-polymerase-beta-germline-variant-confers-cellular-response-to-cisplatin-therapy
#5
Antonia A Nemec, Laura Abriola, Jane S Merkel, Elisa deStanchina, Michelle DeVeaux, Daniel Zelterman, Peter M Glazer, Joann B Sweasy
: Resistance to cancer chemotherapies leads to deadly consequences, yet current research focuses only on the roles of somatically acquired mutations in this resistance. The mutational status of the germline is also likely to play a role in the way cells respond to chemotherapy. The carrier status for the POLB rs3136797 germline mutation encoding P242R DNA polymerase beta (Pol β) is associated with poor prognosis for lung cancer, specifically in response to treatment with cisplatin. Here, it is revealed that the P242R mutation is sufficient to promote resistance to cisplatin in human cells and in mouse xenografts...
January 10, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28067232/oxidized-nucleotide-insertion-by-pol-%C3%AE-confounds-ligation-during-base-excision-repair
#6
Melike Çağlayan, Julie K Horton, Da-Peng Dai, Donna F Stefanick, Samuel H Wilson
Oxidative stress in cells can lead to accumulation of reactive oxygen species and oxidation of DNA precursors. Oxidized purine nucleotides can be inserted into DNA during replication and repair. The main pathway for correcting oxidized bases in DNA is base excision repair (BER), and in vertebrates DNA polymerase β (pol β) provides gap filling and tailoring functions. Here we report that the DNA ligation step of BER is compromised after pol β insertion of oxidized purine nucleotides into the BER intermediate in vitro...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28065385/processing-of-the-abasic-sites-clustered-with-the-benzo-a-pyrene-adducts-by-the-base-excision-repair-enzymes
#7
Lidia V Starostenko, Nadejda I Rechkunova, Natalia A Lebedeva, Alexander A Lomzov, Vladimir V Koval, Olga I Lavrik
The major enzyme in eukaryotic cells that catalyzes the cleavage of apurinic/apyrimidinic (AP or abasic) sites is AP endonuclease 1 (APE1) that cleaves the phosphodiester bond on the 5'-side of AP sites. We found that the efficiency of AP site cleavage by APE1 was affected by the benzo[a]pyrenyl-DNA adduct (BPDE-dG) in the opposite strand. AP sites directly opposite of the modified dG or shifted toward the 5' direction were hydrolyzed by APE1 with an efficiency moderately lower than the AP site in the control DNA duplex, whereas AP sites shifted toward the 3' direction were hydrolyzed significantly less efficiently...
December 27, 2016: DNA Repair
https://www.readbyqxmd.com/read/28059856/lack-of-correlation-between-x-ray-repair-cross-complementing-group-1-gene-polymorphisms-and-the-susceptibility-to-colorectal-cancer-in-a-malaysian-cohort
#8
Tze-Pheng Lau, Lay-Hoong Lian, Phaik-Leng Cheah, Lai-Meng Looi, April C Roslani, Khean-Lee Goh, Ping-Chin Lee, Kek-Heng Chua
X-ray repair cross-complementing group 1 (XRCC1) is one of the key components in the base excision repair pathway that repairs erroneous DNA lesions and removes nonbulky base adducts for the maintenance of genome integrity. Studies have revealed that differences in individual DNA repair capacity can impact the interindividual variation in cancer susceptibility, tumour aggressiveness and treatment response. The relationship between XRCC1 and sporadic colorectal cancer (CRC) susceptibility, which is hitherto inconclusive, has been explored in many association studies of different populations...
January 4, 2017: European Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28058700/xrcc1-arg399gln-gene-polymorphism-and-hepatocellular-carcinoma-risk-in-the-italian-population
#9
Concetta Santonocito, Margherita Scapaticci, Bojan Nedovic, Eleonora B Annicchiarico, Donatella Guarino, Emanuele Leoncini, Stefania Boccia, Antonio Gasbarrini, Ettore Capoluongo
BACKGROUND: The human X-ray repair cross-complementing protein 1 (XRCC1) gene encodes for one of the major repair factors involved in base excision repair (BER), which is reported to be associated with the risk of several cancers. A few studies have explored the association between risk of hepatocellular carcinoma (HCC) and single-nucleotide polymorphisms (SNPs) in different DNA repair genes, with contradictory results. The purpose of this study was to evaluate the association between XRCC1 Arg399Gln polymorphism and susceptibility to HCC...
January 2, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28053122/a-semi-protected-oligonucleotide-recombination-assay-for-dna-mismatch-repair-in-vivo-suggests-different-modes-of-repair-for-lagging-strand-mismatches
#10
Eric A Josephs, Piotr E Marszalek
In Escherichia coli, a DNA mismatch repair (MMR) pathway corrects errors that occur during DNA replication by coordinating the excision and re-synthesis of a long tract of the newly-replicated DNA between an epigenetic signal (a hemi-methylated d(GATC) site or a single-stranded nick) and the replication error after the error is identified by protein MutS. Recent observations suggest that this 'long-patch repair' between these sites is coordinated in the same direction of replication by the replisome. Here, we have developed a new assay that uniquely allows us to introduce targeted 'mismatches' directly into the replication fork via oligonucleotide recombination, examine the directionality of MMR, and quantify the nucleotide-dependence, sequence context-dependence, and strand-dependence of their repair in vivo-something otherwise nearly impossible to achieve...
January 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28049704/the-nucleotide-excision-repair-pathway-limits-l1-retrotransposition
#11
Geraldine Servant, Vincent A Streva, Rebecca S Derbes, Madushani I Wijetunge, Marc Neeland, Travis B White, Victoria P Belancio, Astrid M Roy-Engel, Prescott L Deininger
Long interspersed elements 1 (L1) are active mobile elements that constitute almost 17% of the human genome. They amplify through a "copy-and-paste" mechanism termed retrotransposition, and de novo insertions related to these elements have been reported to cause 0.2% of genetic diseases. Our previous data demonstrated that the endonuclease complex ERCC1-XPF, which cleaves a 3' DNA flap structure, limits L1 retrotransposition. Although the ERCC1-XPF endonuclease participates in several different DNA repair pathways, such as single-strand annealing, or in telomere maintenance, its recruitment to DNA lesions is best characterized in the nucleotide excision repair (NER) pathway...
January 2017: Genetics
https://www.readbyqxmd.com/read/28036256/uv-induced-proteolysis-of-rna-polymerase-ii-is-mediated-by-vcp-p97-segregase-and-timely-orchestration-by-cockayne-syndrome-b-protein
#12
Jinshan He, Qianzheng Zhu, Gulzar Wani, Altaf A Wani
RNA polymerase II (RNAPII) acts as a damage sensor for transcription-coupled nucleotide excision repair (TC-NER) and undergoes proteolytic clearance from damaged chromatin by the ubiquitin-proteasome system (UPS). Here, we report that Valosin-containing protein (VCP)/p97, a druggable oncotarget, is essential for RNAPII's proteolytic clearance in mammalian cells. We show that inhibition of VCP/p97, or siRNA-mediated ablation of VCP/p97 and its cofactors UFD1 and UBXD7 severely impairs ultraviolet radiation (UVR)-induced RNAPII degradation...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035050/chromatin-association-of-xrcc5-6-in-the-absence-of-dna-damage-depends-on-the-xpe-gene-product-ddb2
#13
Damiano Fantini, Shuo Huang, John M Asara, Srilata Bagchi, Pradip Raychaudhuri
Damaged DNA-binding protein 2 (DDB2), a nuclear protein, participates in both nucleotide excision repair and mRNA transcription. The transcriptional regulatory function of DDB2 is significant in colon cancer, as it regulates metastasis. To characterize the mechanism by which DDB2 participates in transcription, we investigated the protein partners in colon cancer cells. Here we show that DDB2 abundantly associates with XRCC5/6, not involving CUL4 and DNA-PKcs. A DNA-damaging agent that induces DNA double-stranded breaks (DSBs) does not affect the interaction between DDB2 and XRCC5...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28032397/dna-base-excision-repair-and-nucleotide-excision-repair-synergistically-contribute-to-survival-of-stationary-phase-cells-of-the-fission-yeast-schizosaccharomyces-pombe
#14
Takanori Senoo, Shinji Kawano, Shogo Ikeda
Defects of genome maintenance may causally contribute to aging. In general, base excision repair (BER) is involved in the repair of subtle base lesions and AP sites, and bulky helix-distorting lesions are restored by nucleotide excision repair (NER). Here, we measured the chronological lifespan (CLS) of BER- and NER-deficient mutants of the fission yeast Schizosaccharomyces pombe, and observed the aging process of cells. The CLS of the nth1 (gene for DNA glycosylase/AP lyase) mutant and the rad16 (a homolog of human XPF) mutant were slightly shorter than that of the wild-type (WT) strain...
December 29, 2016: Cell Biology International
https://www.readbyqxmd.com/read/28028171/single-strand-dna-binding-by-the-helix-hairpin-helix-domain-of-xpf-contributes-to-substrate-specificity-of-ercc1-xpf
#15
Devashish Das, Maryam Faridounnia, Lidija Kovacic, Robert Kaptein, Rolf Boelens, Gert E Folkers
The nucleotide excision repair protein complex ERCC1-XPF is required for incision of DNA upstream of the DNA damage. Functional studies have provided insight into the binding of ERCC1-XPF to various DNA substrates. However, since no structure for the ERCC1-XPF-DNA complex has been determined, the mechanism of substrate recognition remains elusive. Here we biochemically characterize the substrate preferences of the Helix-hairpin-Helix domains of XPF and ERCC-XPF and show that the binding to ss/dsDNA junctions is dependent on joint binding to the DNA binding domain of ERCC1 and XPF...
December 27, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28027876/ercc2-xpd-lys751gln-alter-dna-repair-efficiency-of-platinum-induced-dna-damage-through-p53-pathway
#16
Guopei Zhang, Yangyang Guan, Yuejiao Zhao, Tahar van der Straaten, Sha Xiao, Ping Xue, Guolian Zhu, Qiufang Liu, Yuan Cai, Cuihong Jin, Jinghua Yang, Shengwen Wu, Xiaobo Lu
Platinum-based treatment causes Pt-DNA adducts which lead to cell death. The platinum-induced DNA damage is recognized and repaired by the nucleotide excision repair (NER) system of which ERCC2/XPD is a critical enzyme. Single nucleotide polymorphisms in ERCC2/XPD have been found to be associated with platinum resistance. The aim of the present study was to investigate whether ERCC2/XPD Lys751Gln (rs13181) polymorphism is causally related to DNA repair capacity of platinum-induced DNA damage. First, cDNA clones expressing different genotypes of the polymorphism was transfected to an ERCC2/XPD defective CHO cell line (UV5)...
December 24, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28024337/universal-readers-based-on-hydrogen-bonding-or-%C3%AF-%C3%AF-stacking-for-identification-of-dna-nucleotides-in-electron-tunnel-junctions
#17
Sovan Biswas, Suman Sen, JongOne Im, Sudipta Biswas, Predrag Krstic, Brian Ashcroft, Chad Borges, Yanan Zhao, Stuart Lindsay, Peiming Zhang
A reader molecule, which recognizes all the naturally occurring nucleobases in an electron tunnel junction, is required for sequencing DNA by a recognition tunneling (RT) technique, referred to as a universal reader. In the present study, we have designed a series of heterocyclic carboxamides based on hydrogen bonding and a large-sized pyrene ring based on a π-π stacking interaction as universal reader candidates. Each of these compounds was synthesized to bear a thiolated linker for attachment to metal electrodes and examined for their interactions with naturally occurring DNA nucleosides and nucleotides by (1)H NMR, ESI-MS, computational calculations, and surface plasmon resonance...
December 27, 2016: ACS Nano
https://www.readbyqxmd.com/read/28011151/the-cyclopurine-deoxynucleosides-dna-repair-biological-effects-mechanistic-insights-and-unanswered-questions
#18
Philip J Brooks
Patients with the genetic disease xeroderma pigmentosum (XP) who lack the capacity to carry out nucleotides excision repair (NER) have a dramatically elevated risk of skin cancer on sun exposed areas of the body. NER is the DNA repair mechanism responsible for the removal of DNA lesions resulting from ultraviolet light. In addition, a subset of XP patients develop a progressive neurodegenerative disease, referred to as XP neurologic disease, which is thought to be the result of accumulation of endogenous DNA lesions that are repaired by NER but not other repair pathways...
December 21, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27994662/tfiih-new-discoveries-regarding-its-mechanisms-and-impact-on-cancer-treatment
#19
REVIEW
Mario Zurita, Grisel Cruz-Becerra
The deregulation of gene expression is a characteristic of cancer cells, and malignant cells require very high levels of transcription to maintain their cancerous phenotype and survive. Therefore, components of the basal transcription machinery may be considered as targets to preferentially kill cancerous cells. TFIIH is a multisubunit basal transcription factor that also functions in nucleotide excision repair. The recent discoveries of some small molecules that interfere with TFIIH and that preferentially kill cancer cells have increased researchers' interest to elucidate the complex mechanisms by which TFIIH operates...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27989139/unpredicted-downregulation-of-rad51-suggests-genome-instability-induced-by-tetrachlorobenzoquinone
#20
Xiufang Song, Qiong Shi, Zixuan Liu, Yawen Wang, Yuxin Wang, Erqun Song, Yang Song
We previously demonstrated that halogenated quinone induces DNA double strand breaks (DSBs) in a ROS-dependent manner, which coordinates with downstream repair cascade including nonhomologous end joining, base excision repair, and nucleotide excision repair. However, these error-prone processes may cause the potential risk of genome instability, and current has no information on how faithful repair route, such as homologous recombination (HR), was affected. RAD51 is a key protein in the HR pathway of DSBs repair...
December 19, 2016: Chemical Research in Toxicology
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