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nucleotide excision repair

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https://www.readbyqxmd.com/read/28645711/proteome-dynamics-during-post-desiccation-recovery-reveal-convergence-of-desiccation-and-gamma-radiation-stress-response-pathways-in-deinococcus-radiodurans
#1
Aman Kumar Ujaoney, Mahesh Kumar Padwal, Bhakti Basu
Deinococcus radiodurans is inherently resistant to both ionizing radiation and desiccation. Fifteen months of desiccation was found to be the LD50 dose for D. radiodurans. Desiccated cells of D. radiodurans entered 6h of growth arrest during post-desiccation recovery (PDR). Proteome dynamics during PDR were mapped by resolving cellular proteins by 2-dimensional gel electrophoresis coupled with mass spectrometry. At least 41 proteins, represented by 51 spots on proteome profiles, were differentially expressed throughout PDR...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28645369/sequencing-dna-for-the-oxidatively-modified-base-8-oxo-7-8-dihydroguanine
#2
Aaron M Fleming, Yun Ding, Cynthia J Burrows
The DNA base guanine (G) can be oxidatively modified to 8-oxo-7,8-dihydroguanine (OG). Extraction of genomic DNA followed by nuclease digestion and mass spectrometry analysis has found OG is present at background levels of ~1 out of 10(6) Gs; however, this approach cannot determine the locations for the OGs in the genome. Thus, in this methods report, we outline three different methods (A, B, and C) for sequencing OG in DNA. Method A sequences OG by utilizing the base excision repair pathway to delete the OG nucleotide from the DNA that is then detected by Sanger sequencing as a deletion signature...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28630130/how-a-genetically-stable-extremophile-evolves-modes-of-genome-diversification-in-the-archaeon-sulfolobus-acidocaldarius
#3
Dominic Mao, Dennis W Grogan
In order to analyze in molecular terms how Sulfolobus genomes diverge, damage-induced mutations and natural polymorphisms (PMs) were identified in laboratory constructs and wild-type isolates, respectively, of Sulfolobus acidocaldarius Among wild-type isolates drawn from one local population, pairwise nucleotide divergence averaged 4 x 10(-6), which is about 0.15% of the corresponding divergence reported for Sulfolobus islandicus The most variable features of wild-type S. acidocaldarius genomes were homopolymer (mononucleotide) tracts and longer tandem repeats, consistent with the spontaneous mutations that occur under laboratory conditions...
June 19, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28621520/homogeneously-sensitive-detection-of-multiple-dna-glycosylases-with-intrinsically-fluorescent-nucleotides
#4
Yan Zhang, Chen-Chen Li, Bo Tang, Chun-Yang Zhang
DNA glycosylases are responsible for recognition and excision of the damaged bases in the base excision repair pathway, and all mammals express multiple DNA glycosylases to maintain genome stability. However, simultaneous detection of multiple DNA glycosylase still remains a great challenge. Here, we develop a rapid and sensitive fluorescent method for simultaneous detection of uracil DNA glycolase (UDG) and human 8-oxoG DNA glycosylase 1 (hOGG1) using exonuclease-assisted recycling signal amplification in combination with fluorescent bases 2-aminopurine (2-AP) and pyrrolo-dC (P-dC) as the fluorophores...
June 16, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28615972/single-nucleotide-polymorphisms-and-unacceptable-late-toxicity-in-breast-cancer-adjuvant-radiotherapy-a-case-report
#5
Grazia Lazzari, Maria Iole Natalicchio, Angela Terlizzi, Francesco Perri, Giovanni Silvano
BACKGROUND: There has recently been a strong interest in the inter-individual variation in normal tissue and tumor response to radiotherapy (RT), because tissue radiosensitivity seems to be under genetic control. Evidence is accumulating on the role of polymorphic genetic variants, such as single nucleotide polymorphisms (SNPs) that could influence normal tissue response after radiation. The most studied SNPs include those in genes involved in DNA repair (single- and double-strand breaks, and base excision) and those active in the response to oxidative stress...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28608017/relationship-between-expression-of-proteins-ercc1-ercc2-and-xrcc1-and-clinical-outcomes-in-patients-with-rectal-cancer-treated-with-folfox-based-preoperative-chemoradiotherapy
#6
Ming-Yii Huang, Joh-Jong Huang, Chun-Ming Huang, Chih-Hung Lin, Hsiang-Lin Tsai, Ching-Wen Huang, Chee-Yin Chai, Chia-Yang Lin, Jaw-Yuan Wang
BACKGROUND: Platinum resistance enhances DNA damage repair through nucleotide excision repair mechanisms involving the excision repair cross-complementing group 1 (ERCC1), X-ray cross-complementing group 1 (XRCC1), and excision repair cross-complementing group 2 (ERCC2). We evaluated the correlation between the expression of these three DNA repair genes and clinical outcomes in patients with rectal cancer receiving FOLFOX-based preoperative chemoradiotherapy (CRT). METHODS: Using immunohistochemistry, we examined the expression of ERCC1, ERCC2, and XRCC1 in pre-CRT cancer tissues from 86 patients with rectal cancer who had undergone curative resection and preoperative CRT with FOLFOX-4 to identify potential predictors of clinical outcomes...
June 12, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/28607063/dynamic-maps-of-uv-damage-formation-and-repair-for-the-human-genome
#7
Jinchuan Hu, Ogun Adebali, Sheera Adar, Aziz Sancar
Formation and repair of UV-induced DNA damage in human cells are affected by cellular context. To study factors influencing damage formation and repair genome-wide, we developed a highly sensitive single-nucleotide resolution damage mapping method [high-sensitivity damage sequencing (HS-Damage-seq)]. Damage maps of both cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] from UV-irradiated cellular and naked DNA revealed that the effect of transcription factor binding on bulky adducts formation varies, depending on the specific transcription factor, damage type, and strand...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28607059/human-genome-wide-repair-map-of-dna-damage-caused-by-the-cigarette-smoke-carcinogen-benzo-a-pyrene
#8
Wentao Li, Jinchuan Hu, Ogun Adebali, Sheera Adar, Yanyan Yang, Yi-Ying Chiou, Aziz Sancar
Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon, is the major cause of lung cancer. BaP forms covalent DNA adducts after metabolic activation and induces mutations. We have developed a method for capturing oligonucleotides carrying bulky base adducts, including UV-induced cyclobutane pyrimidine dimers (CPDs) and BaP diol epoxide-deoxyguanosine (BPDE-dG), which are removed from the genome by nucleotide excision repair. The isolated oligonucleotides are ligated to adaptors, and after damage-specific immunoprecipitation, the adaptor-ligated oligonucleotides are converted to dsDNA with an appropriate translesion DNA synthesis (TLS) polymerase, followed by PCR amplification and next-generation sequencing (NGS) to generate genome-wide repair maps...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28599464/dna-repair-genes-polymorphisms-and-genetic-susceptibility-to-philadelphia-negative-myeloproliferative-neoplasms-in-a-portuguese-population-the-role-of-base-excision-repair-genes-polymorphisms
#9
Ana P Azevedo, Susana N Silva, João P De Lima, Alice Reichert, Fernando Lima, Esmeraldina Júnior, José Rueff
The role of base excision repair (BER) genes in Philadelphia-negative (PN)-myeloproliferative neoplasms (MPNs) susceptibility was evaluated by genotyping eight polymorphisms [apurinic/apyrimidinic endodeoxyribonuclease 1, mutY DNA glycosylase, earlier mutY homolog (E. coli) (MUTYH), 8-oxoguanine DNA glycosylase 1, poly (ADP-ribose) polymerase (PARP) 1, PARP4 and X-ray repair cross-complementing 1 (XRCC1)] in a case-control study involving 133 Caucasian Portuguese patients. The results did not reveal a correlation between individual BER polymorphisms and PN-MPNs when considered as a whole...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28592488/dna-damage-induced-atr-kinase-activation-in-non-replicating-cells-is-regulated-by-the-xpb-subunit-of-transcription-factor-ii-h-tfiih
#10
Michael G Kemp
The role of the DNA damage response protein kinase ataxia telangiectasia and Rad-3-related (ATR) in the cellular response to DNA damage during the replicative phase of the cell cycle has been extensively studied. However, little is known about ATR kinase function in cells that are not actively replicating DNA and which constitute most cells in the human body. Using small-molecule inhibitors of ATR kinase and overexpression of a kinase-inactive form of the enzyme, I show here that ATR promotes cell death in non-replicating/non-cycling cultured human cells exposed to N-acetoxy-2-acetylaminofluorene (NA-AAF), which generates bulky DNA adducts that block RNA polymerase movement...
June 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28588253/nucleotide-excision-repair-ner-is-a-potential-therapeutic-target-in-multiple-myeloma
#11
R Szalat, M K Samur, M Fulciniti, M Lopez, P Nanjappa, A Cleynen, K Wen, S Kumar, T Perrini, A S Calkins, E Reznichenko, D Chauhan, Y-T Tai, M Shammas, J-P Fermand, B Arnulf, H Avet-Loiseau, J-B Lazaro, N C Munshi
Nucleotide excision repair is active in multiple myeloma cells.Inhibition of NER increases sensitivity to alkylating agent.NER is a potential target for multiple myeloma treatment. Despite the development of novel drugs, alkylating agents remain an important component of therapy in multiple myeloma (MM). DNA repair processes contribute towards sensitivity to alkylating agents, therefore we here evaluate the role of nucleotide excision repair (NER) which is involved in the removal of bulky adducts and DNA crosslinks in MM...
June 7, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28570512/atomic-force-microscopy-investigations-of-dna-lesion-recognition-in-nucleotide-excision-repair
#12
Jonas Gross, Nicolas Wirth, Ingrid Tessmer
AFM imaging is a powerful technique for the study of protein-DNA interactions. This single molecule method allows the simultaneous resolution of different molecules and molecular assemblies in a heterogeneous sample. In the particular context of DNA interacting protein systems, different protein complex forms and their corresponding binding positions on target sites containing DNA fragments can thus be distinguished. Here, an application of AFM to the study of DNA lesion recognition in the prokaryotic and eukaryotic nucleotide excision DNA repair (NER) systems is presented...
May 24, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28562347/epistatic-snp-interaction-of-ercc6-with-ercc8-and-their-joint-protein-expression-contribute-to-gastric-cancer-atrophic-gastritis-risk
#13
Jing-Jing Jing, You-Zhu Lu, Li-Ping Sun, Jing-Wei Liu, Yue-Hua Gong, Qian Xu, Nan-Nan Dong, Yuan Yuan
Excision repair cross-complementing group 6 and 8 (ERCC6 and ERCC8) are two indispensable genes for the initiation of transcription-coupled nucleotide excision repair pathway. This study aimed to evaluate the interactions between single nucleotide polymorphisms of ERCC6 (rs1917799) and ERCC8 (rs158572 and rs158916) in gastric cancer and its precancerous diseases. Besides, protein level analysis were performed to compare ERCC6 and ERCC8 expression in different stages of gastric diseases, and to correlate SNPs jointly with gene expression...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28559431/dna-polymerase-beta-participates-in-mitochondrial-dna-repair
#14
P Sykora, S Kanno, M Akbari, T Kulikowicz, B A Baptiste, G S Leandro, H Lu, J Tian, A May, K A Becker, D L Croteau, D M Wilson, R W Sobol, A Yasui, V A Bohr
We have detected DNA polymerase beta (Polβ), known as a key nuclear base excision repair (BER) protein, in mitochondrial protein extracts derived from mammalian tissue and cells. Manipulation of the N-terminal sequence affected the amount of Polβ in the mitochondria. Using Polβ fragments, mitochondrial-specific protein partners were identified, with the interactors mainly functioning in DNA maintenance and mitochondrial import. Of particular interest was the identification of the proteins TWINKLE, SSBP1 and TFAM, all of which are mitochondria specific DNA effectors and are known to function in the nucleoid...
May 30, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28554534/ophthalmic-manifestations-of-xeroderma-pigmentosum-a-perspective-from-the-united-kingdom
#15
Rongxuan Lim, Mieran Sethi, Ana M S Morley
PURPOSE: To document the ocular manifestations of xeroderma pigmentosum (XP), presenting via the United Kingdom (UK) XP service, and to analyze the correlations between XP genotype and ophthalmic phenotype. DESIGN: Prospective observational case series. SUBJECTS: Eighty-nine patients seen by the UK Nationally Commissioned XP Service, from April 2010 to December 2014, with a genetically confirmed diagnosis of XP. METHODS: Patients underwent a full ophthalmic examination at each visit...
May 26, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28552776/differential-sensitivities-of-cellular-xpa-and-parp-1-to-arsenite-inhibition-and-zinc-rescue
#16
Xiaofeng Ding, Xixi Zhou, Karen L Cooper, Juliana Huestis, Laurie G Hudson, Ke Jian Liu
Arsenite directly binds to the zinc finger domains of the DNA repair protein poly (ADP ribose) polymerase (PARP)-1, and inhibits PARP-1 activity in the base excision repair (BER) pathway. PARP inhibition by arsenite enhances ultraviolet radiation (UVR)-induced DNA damage in keratinocytes, and the increase in DNA damage is reduced by zinc supplementation. However, little is known about the effects of arsenite and zinc on the zinc finger nucleotide excision repair (NER) protein xeroderma pigmentosum group A (XPA)...
May 25, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28521214/def1-and-dst1-play-distinct-roles-in-repair-of-ap-lesions-in-highly-transcribed-genomic-regions
#17
Norah Owiti, Christopher Lopez, Shivani Singh, Andrei Stephenson, Nayun Kim
Abasic or AP sites generated by spontaneous DNA damage accumulate at a higher rate in actively transcribed regions of the genome in S. cerevisiae and are primarily repaired by base excision repair (BER) pathway. We have demonstrated that transcription-coupled nucleotide excision repair (NER) pathway can functionally replace BER to repair those AP sites located on the transcribed strand much like the strand specific repair of UV-induced pyrimidine dimers. Previous reports indicate that Rad26, a yeast homolog of transcription-repair coupling factor CSB, partly mediates strand-specific repair of UV-dimers as well as AP lesions...
May 10, 2017: DNA Repair
https://www.readbyqxmd.com/read/28514164/the-nonbulky-dna-lesions-spiroiminodihydantoin-and-5-guanidinohydantoin-significantly-block-human-rna-polymerase-ii-elongation-in-vitro
#18
Marina Kolbanovskiy, Moinuddin A Chowdhury, Aditi Nadkarni, Suse Broyde, Nicholas E Geacintov, David A Scicchitano, Vladimir Shafirovich
The most common, oxidatively generated lesion in cellular DNA is 8-oxo-7,8-dihydroguanine, which can be oxidized further to yield highly mutagenic spiroiminodihydantoin (Sp) and 5-guanidinohydantoin (Gh) in DNA. In human cell-free extracts, both lesions can be excised by base excision repair and global genomic nucleotide excision repair. However, it is not known if these lesions can be removed by transcription-coupled DNA repair (TCR), a pathway that clears lesions from DNA that impede RNA synthesis. To determine if Sp or Gh impedes transcription, which could make each a viable substrate for TCR, either an Sp or a Gh lesion was positioned on the transcribed strand of DNA under the control of a promoter that supports transcription by human RNA polymerase II...
June 7, 2017: Biochemistry
https://www.readbyqxmd.com/read/28509359/the-dna-translocase-rad5a-acts-independently-of-the-other-main-dna-repair-pathways-and-requires-both-its-atpase-and-ring-domain-for-activity-in-arabidopsis-thaliana
#19
Tobias Klemm, Anja Mannuß, Daniela Kobbe, Alexander Knoll, Oliver Trapp, Annika Dorn, Holger Puchta
Multiple pathways exist to repair DNA damage induced by methylating and cross-linking agents in Arabidopsis thaliana. The SWI2/SNF2 translocase RAD5A, the functional homolog of budding yeast Rad5 that is required for the error-free branch of post replicative repair, plays a surprisingly prominent role in the repair of both kinds of lesions in Arabidopsis. Here we show that both the ATPase domain and the ubiquitination function of the RING domain of the Arabidopsis protein are essential for the cellular response to different forms of DNA damage...
May 16, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28493484/cytoplasmic-overexpression-of-rna-binding-protein-hur-is-a-marker-of-poor-prognosis-in-meningioma-and-hur-knockdown-decreases-meningioma-cell-growth-and-resistance-to-hypoxia
#20
Guillaume Gauchotte, Sébastien Hergalant, Charlène Vigouroux, Jean-Matthieu Casse, Rémi Houlgatte, Tony Kaoma, Déborah Helle, Lydia Brochin, Fabien Rech, Matthieu Peyre, François Labrousse, Laurent Vallar, Jean-Louis Gueant, Jean-Michel Vignaud, Shyue-Fang Battaglia-Hsu
HuR regulates cytoplasmic mRNA stability and translatability, and the HuR expression level has been shown to correlate with poor disease outcome in several cancer types; however, the prognostic value and potential pro-oncogenic properties of HuR in meningioma remain unclear. Thus, in the present study we analyzed 85 meningioma tissue samples to establish the relationship between HuR expression, tumor-cell proliferation, and/or patient survival. In addition, we examined the anti-proliferative effects of HuR knockdown in two meningioma cell lines (IOMM-Lee and Ben-Men1), and conducted transcriptome-wide analyses (IOMM-Lee cells) to elucidate the molecular consequences of HuR knockdown...
May 11, 2017: Journal of Pathology
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