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[PMID]: 28575236 [Au] Autor: Bj Rås KØ; Sousa MML; Sharma A; Fonseca DM; S Gaard CK; Bj Rås M; Otterlei M [Ad] Endereço: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway. [Ti] Título: Monitoring of the spatial and temporal dynamics of BER/SSBR pathway proteins, including MYH, UNG2, MPG, NTH1 and NEIL1-3, during DNA replication. [So] Source: Nucleic Acids Res;45(14):8291-8301, 2017 Aug 21. [Is] ISSN: 1362-4962 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Base lesions in DNA can stall the replication machinery or induce mutations if bypassed. Consequently, lesions must be repaired before replication or in a post-replicative process to maintain genomic stability. Base excision repair (BER) is the main pathway for repair of base lesions and is known to be associated with DNA replication, but how BER is organized during replication is unclear. Here we coupled the iPOND (isolation of proteins on nascent DNA) technique with targeted mass-spectrometry analysis, which enabled us to detect all proteins required for BER on nascent DNA and to monitor their spatiotemporal orchestration at replication forks. We demonstrate that XRCC1 and other BER/single-strand break repair (SSBR) proteins are enriched in replisomes in unstressed cells, supporting a cellular capacity of post-replicative BER/SSBR. Importantly, we identify for the first time the DNA glycosylases MYH, UNG2, MPG, NTH1, NEIL1, 2 and 3 on nascent DNA. Our findings suggest that a broad spectrum of DNA base lesions are recognized and repaired by BER in a post-replicative process. [Mh] Termos MeSH primário: Quebras de DNA de Cadeia Simples Enzimas Reparadoras do DNA/metabolismo Reparo do DNA Replicação do DNA DNA/genética [Mh] Termos MeSH secundário: Linhagem Celular Tumoral DNA/metabolismo DNA Glicosilases/metabolismo DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo Proteínas de Ligação a DNA/metabolismo Desoxirribonuclease (Dímero de Pirimidina)/metabolismo Células HEK293 Células HeLa Seres Humanos Immunoblotting Espectrometria de Massas/métodos N-Glicosil Hidrolases/metabolismo Transdução de Sinais/genética Fatores de Tempo Proteína 1 Complementadora Cruzada de Reparo de Raio-X [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (DNA-Binding Proteins); 0 (X-ray Repair Cross Complementing Protein 1); 0 (XRCC1 protein, human); 9007-49-2 (DNA); EC 3.1.25.1 (Deoxyribonuclease (Pyrimidine Dimer)); EC 3.1.25.1 (NTHL1 protein, human); EC 3.2.2.- (CCNO protein, human); EC 3.2.2.- (DNA Glycosylases); EC 3.2.2.- (FLJ10858 protein, human); EC 3.2.2.- (N-Glycosyl Hydrolases); EC 3.2.2.- (NEIL1 protein, human); EC 3.2.2.- (mutY adenine glycosylase); EC 3.2.2.21 (DNA-3-methyladenine glycosidase II); EC 4.2.99.18 (DNA-(Apurinic or Apyrimidinic Site) Lyase); EC 4.2.99.18 (NEIL2 protein, human); EC 6.5.1.- (DNA Repair Enzymes) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170603 [St] Status: MEDLINE [do] DOI: 10.1093/nar/gkx476

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[PMID]: 28475923 [Au] Autor: Pérez-Iglesias JM; Ruiz de Arcaute C; Natale GS; Soloneski S; Larramendy ML [Ad] Endereço: Cátedra de Citología, Facultad de Ciencias Naturales y Museo, Universidad Nacional de La Plata, Calle 64 No 3, B1904AMA La Plata, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. [Ti] Título: Evaluation of imazethapyr-induced DNA oxidative damage by alkaline Endo III- and Fpg-modified single-cell gel electrophoresis assay in Hypsiboas pulchellus tadpoles (Anura, Hylidae). [So] Source: Ecotoxicol Environ Saf;142:503-508, 2017 Aug. [Is] ISSN: 1090-2414 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Imazethapyr (IMZT) is a selective postemergent herbicide with residual action. Available data analyzing its effects in aquatic vertebrates are scarce. In previous studies, we demonstrated that IMZT induces lesions into the DNA of Hypsiboas pulchellus tadpoles using the single-cell gel electrophoresis (SCGE) assay as a biomarker for genotoxicity. Currently, this assay can be modified by including incubation with lesion-specific endonucleases, e.g., endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg), which detect oxidized pyrimidine and purine bases, respectively. The aim of this study was to evaluate the role of oxidative stress in the genotoxic damage in circulating blood cells of H. pulchellus tadpoles exposed to the IMZT-based Pivot H formulation (10.59% IMZT) at a concentration equivalent to 25% of the LC (96h) value (0.39mg/L IMZT) during 48 and 96h. Our results demonstrate that the herbicide induces oxidative DNA damage on H. pulchellus tadpoles at purines bases but not at pyrimidines. Our findings represent the first evidence of oxidative damage caused by IMZT on anuran DNA using the alkaline restriction enzyme-modified SCGE assay. [Mh] Termos MeSH primário: Dano ao DNA Herbicidas/toxicidade Mutagênicos/toxicidade Ácidos Nicotínicos/toxicidade Estresse Oxidativo/efeitos dos fármacos Poluentes Químicos da Água/toxicidade [Mh] Termos MeSH secundário: Animais Anuros Ensaio Cometa DNA-Formamidopirimidina Glicosilase/química Desoxirribonuclease (Dímero de Pirimidina)/química Proteínas de Escherichia coli/química Larva/efeitos dos fármacos Oxirredução Estresse Oxidativo/genética [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Escherichia coli Proteins); 0 (Herbicides); 0 (Mutagens); 0 (Nicotinic Acids); 0 (Water Pollutants, Chemical); 72T2IN94I4 (imazethapyr); EC 3.1.25.1 (Deoxyribonuclease (Pyrimidine Dimer)); EC 3.1.25.1 (NTH protein, E coli); EC 3.2.2.23 (DNA-Formamidopyrimidine Glycosylase) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170506 [St] Status: MEDLINE

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[PMID]: 28292631 [Au] Autor: Robey-Bond SM; Benson MA; Barrantes-Reynolds R; Bond JP; Wallace SS [Ad] Endereço: Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405-0068, United States. [Ti] Título: Probing the activity of NTHL1 orthologs by targeting conserved amino acid residues. [So] Source: DNA Repair (Amst);53:43-51, 2017 May. [Is] ISSN: 1568-7856 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: The base excision repair DNA glycosylases, EcoNth and hNTHL1, are homologous, with reported overlapping yet different substrate specificities. The catalytic amino acid residues are known and are identical between the two enzymes although the exact structures of the substrate binding pockets remain to be determined. We sought to explore the sequence basis of substrate differences using a phylogeny-based design of site-directed mutations. Mutations were made for each enzyme in the vicinity of the active site and we examined these variants for glycosylase and lyase activity. Single turnover kinetics were done on a subgroup of these, comparing activity on two lesions, 5,6-dihydrouracil and 5,6-dihydrothymine, with different opposite bases. We report that wild type hNTHL1 and EcoNth are remarkably alike with respect to the specificity of the glycosylase reaction, and although hNTHL1 is a much slower enzyme than EcoNth, the tighter binding of hNTHL1 compensates, resulting in similar k /K values for both enzymes with each of the substrates tested. For the hNTHL1 variant Gln287Ala, the specificity for substrates positioned opposite G is lost, but not that of substrates positioned opposite A, suggesting a discrimination role for this residue. The EcoNth Thr121 residue influences enzyme binding to DNA, as binding is significantly reduced with the Thr121Ala variant. Finally, we present evidence that hNTHL1 Asp144, unlike the analogous EcoNth residue Asp44, may be involved in resolving the glycosylase transition state. [Mh] Termos MeSH primário: Domínio Catalítico Dano ao DNA Desoxirribonuclease (Dímero de Pirimidina)/metabolismo Proteínas de Escherichia coli/metabolismo Mutação [Mh] Termos MeSH secundário: Sequência de Aminoácidos DNA/metabolismo Desoxirribonuclease (Dímero de Pirimidina)/genética Escherichia coli/enzimologia Proteínas de Escherichia coli/genética Seres Humanos Cinética Especificidade por Substrato [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Escherichia coli Proteins); 9007-49-2 (DNA); EC 3.1.25.1 (Deoxyribonuclease (Pyrimidine Dimer)); EC 3.1.25.1 (NTH protein, E coli); EC 3.1.25.1 (NTHL1 protein, human) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170728 [Lr] Data última revisão: 170728 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170316 [St] Status: MEDLINE

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[PMID]: 28271350 [Au] Autor: Soloneski S; Ruiz de Arcaute C; Nikoloff N; Larramendy ML [Ad] Endereço: Cátedra de Citología, Facultad de Ciencias Naturales y Museo, Universidad Nacional de La Plata, Calle 64 Nro. 3 (esq. 120), B1904AMA, La Plata, Argentina. [Ti] Título: Genotoxicity of the herbicide imazethapyr in mammalian cells by oxidative DNA damage evaluation using the Endo III and FPG alkaline comet assays. [So] Source: Environ Sci Pollut Res Int;24(11):10292-10300, 2017 Apr. [Is] ISSN: 1614-7499 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: We evaluated the role of oxidative stress in the genotoxic damage induced by imazethapyr (IMZT) and its formulation Pivot® in mammalian CHO-K1 cell line. Using the alkaline comet assay, we observed that a concentration of 0.1 µg/mL of IMZT or Pivot® was able to induce DNA damage by increasing the frequency of damaged nucleoids. To test whether the DNA lesions were caused by oxidative stress, the DNA repair enzymes endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg), which convert base damage to strand breaks, were used. Our results demonstrate that after treatment of CHO-K1 cells with the pure active ingredient as well as the commercial formulation Pivot®, an increase in DNA strand breaks was observed after incubation of both Endo III and Fpg enzymes, indicating that both compounds induce DNA damage involving both pyrimidine and purine-based oxidations, at least in CHO-K1 cells. Our findings confirm the genotoxic potential of IMZT and suggest that this herbicide formulation must be employed with great caution, especially not only for exposed occupational workers but also for other living species. [Mh] Termos MeSH primário: Ensaio Cometa Dano ao DNA Herbicidas/toxicidade Ácidos Nicotínicos/toxicidade [Mh] Termos MeSH secundário: Animais Desoxirribonuclease (Dímero de Pirimidina) Proteínas de Escherichia coli Estresse Oxidativo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Escherichia coli Proteins); 0 (Herbicides); 0 (Nicotinic Acids); 72T2IN94I4 (imazethapyr); EC 3.1.25.1 (Deoxyribonuclease (Pyrimidine Dimer)); EC 3.1.25.1 (NTH protein, E coli) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170309 [St] Status: MEDLINE [do] DOI: 10.1007/s11356-017-8666-5

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[PMID]: 28011748 [Au] Autor: Li Y; Yan J; Ding W; Chen Y; Pack LM; Chen T [Ad] Endereço: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR 72079, USA. [Ti] Título: Genotoxicity and gene expression analyses of liver and lung tissues of mice treated with titanium dioxide nanoparticles. [So] Source: Mutagenesis;32(1):33-46, 2017 Jan. [Is] ISSN: 1464-3804 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Titanium dioxide nanoparticles (TiO NPs) are used in paints, plastics, papers, inks, foods, toothpaste, pharmaceuticals and cosmetics. However, TiO NPs cause inflammation, pulmonary damage, fibrosis and lung tumours in animals and are possibly carcinogenic to humans. Although there are a large number of studies on the toxicities of TiO NPs, the data are inconclusive and the mechanisms underlying the toxicity are not clear. In this study, we used the Comet assay to evaluate genotoxicity and whole-genome microarray technology to analyse gene expression pattern in vivo to explore the possible mechanisms for toxicity and genotoxicity of TiO NPs. Mice were treated with three daily i.p. injections of 50 mg/kg 10 nm anatase TiO NPs and sacrificed 4 h after the last treatment. The livers and lungs were then isolated for the Comet assay and whole genome microarray analysis of gene expression. The NPs were heavily accumulated in liver and lung tissues. However, the treatment was positive for DNA strand breaks only in liver measured with the standard Comet assay, but positive for oxidative DNA adducts in both liver and lung as determined with the enzyme-modified Comet assay. The genotoxicity results suggest that DNA damage mainly resulted from oxidised nucleotides. Gene expression profiles and functional analyses revealed that exposure to TiO NPs triggered distinct gene expression patterns in both liver and lung tissues. The gene expression results suggest that TiO NPs impair DNA and cells by interrupting metabolic homeostasis in liver and by inducing oxidative stress, inflammatory responses and apoptosis in lung. These findings have broad implications when evaluating the safety of TiO NPs used in numerous consumer products. [Mh] Termos MeSH primário: Dano ao DNA Fígado/efeitos dos fármacos Pulmão/efeitos dos fármacos Nanopartículas Metálicas/toxicidade Titânio/toxicidade [Mh] Termos MeSH secundário: Animais Ensaio Cometa DNA/efeitos dos fármacos DNA Glicosilases Desoxirribonuclease (Dímero de Pirimidina) Proteínas de Escherichia coli Perfilação da Expressão Gênica Injeções Intraperitoneais Fígado/metabolismo Pulmão/metabolismo Masculino Nanopartículas Metálicas/administração & dosagem Nanopartículas Metálicas/química Camundongos Estresse Oxidativo/efeitos dos fármacos Titânio/administração & dosagem Titânio/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Escherichia coli Proteins); 15FIX9V2JP (titanium dioxide); 9007-49-2 (DNA); D1JT611TNE (Titanium); EC 3.1.25.1 (Deoxyribonuclease (Pyrimidine Dimer)); EC 3.1.25.1 (NTH protein, E coli); EC 3.2.2.- (DNA Glycosylases); EC 3.2.2.- (oxoguanine glycosylase 1, human) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170825 [Lr] Data última revisão: 170825 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161225 [St] Status: MEDLINE [do] DOI: 10.1093/mutage/gew065

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[PMID]: 27713038 [Au] Autor: Broderick P; Dobbins SE; Chubb D; Kinnersley B; Dunlop MG; Tomlinson I; Houlston RS [Ad] Endereço: Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. [Ti] Título: Validation of Recently Proposed Colorectal Cancer Susceptibility Gene Variants in an Analysis of Families and Patients-a Systematic Review. [So] Source: Gastroenterology;152(1):75-77.e4, 2017 Jan. [Is] ISSN: 1528-0012 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: High-throughput sequencing analysis has accelerated searches for genes associated with risk for colorectal cancer (CRC); germline mutations in NTHL1, RPS20, FANCM, FAN1, TP53, BUB1, BUB3, LRP6, and PTPN12 have been recently proposed to increase CRC risk. We attempted to validate the association between variants in these genes and development of CRC in a systematic review of 11 publications, using sequence data from 863 familial CRC cases and 1604 individuals without CRC (controls). All cases were diagnosed at an age of 55 years or younger and did not carry mutations in an established CRC predisposition gene. We found sufficient evidence for NTHL1 to be considered a CRC predisposition gene-members of 3 unrelated Dutch families were homozygous for inactivating p.Gln90Ter mutations; a Canadian woman with polyposis, CRC, and multiple tumors was reported to be heterozygous for the inactivating NTHL1 p.Gln90Ter/c.709+1G>A mutations; and a man with polyposis was reported to carry p.Gln90Ter/p.Gln287Ter; whereas no inactivating homozygous or compound heterozygous mutations were detected in controls. Variants that disrupted RPS20 were detected in a Finnish family with early-onset CRC (p.Val50SerfsTer23), a 39-year old individual with metachronous CRC (p.Leu61GlufsTer11 mutation), and a 41-year-old individual with CRC (missense p.Val54Leu), but not in controls. We therefore found published evidence to support the association between variants in NTHL1 and RPS20 with CRC, but not of other recently reported CRC susceptibility variants. We urge the research community to adopt rigorous statistical and biological approaches coupled with independent replication before making claims of pathogenicity. [Mh] Termos MeSH primário: Polipose Adenomatosa do Colo/genética Neoplasias Colorretais/genética Desoxirribonuclease (Dímero de Pirimidina)/genética Predisposição Genética para Doença/genética Proteínas Ribossômicas/genética [Mh] Termos MeSH secundário: Mutação em Linhagem Germinativa Seres Humanos [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW; VALIDATION STUDIES [Nm] Nome de substância: 0 (Ribosomal Proteins); 0 (ribosomal protein S20); EC 3.1.25.1 (Deoxyribonuclease (Pyrimidine Dimer)); EC 3.1.25.1 (NTHL1 protein, human) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170613 [Lr] Data última revisão: 170613 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 161008 [St] Status: MEDLINE

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[PMID]: 27839712 [Au] Autor: Swartzlander DB; McPherson AJ; Powers HR; Limpose KL; Kuiper EG; Degtyareva NP; Corbett AH; Doetsch PW [Ad] Endereço: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, United States; Graduate Program in Genetics and Molecular Biology, Emory University School of Medicine, Atlanta, GA 30322, United States. [Ti] Título: Identification of SUMO modification sites in the base excision repair protein, Ntg1. [So] Source: DNA Repair (Amst);48:51-62, 2016 Dec. [Is] ISSN: 1568-7856 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: DNA damaging agents are a constant threat to genomes in both the nucleus and the mitochondria. To combat this threat, a suite of DNA repair pathways cooperate to repair numerous types of DNA damage. If left unrepaired, these damages can result in the accumulation of mutations which can lead to deleterious consequences including cancer and neurodegenerative disorders. The base excision repair (BER) pathway is highly conserved from bacteria to humans and is primarily responsible for the removal and subsequent repair of toxic and mutagenic oxidative DNA lesions. Although the biochemical steps that occur in the BER pathway have been well defined, little is known about how the BER machinery is regulated. The budding yeast, Saccharomyces cerevisiae is a powerful model system to biochemically and genetically dissect BER. BER is initiated by DNA N-glycosylases, such as S. cerevisiae Ntg1. Previous work demonstrates that Ntg1 is post-translationally modified by SUMO in response to oxidative DNA damage suggesting that this modification could modulate the function of Ntg1. In this study, we mapped the specific sites of SUMO modification within Ntg1 and identified the enzymes responsible for sumoylating/desumoylating Ntg1. Using a non-sumoylatable version of Ntg1, ntg1ΔSUMO, we performed an initial assessment of the functional impact of Ntg1 SUMO modification in the cellular response to DNA damage. Finally, we demonstrate that, similar to Ntg1, the human homologue of Ntg1, NTHL1, can also be SUMO-modified in response to oxidative stress. Our results suggest that SUMO modification of BER proteins could be a conserved mechanism to coordinate cellular responses to DNA damage. [Mh] Termos MeSH primário: Reparo do DNA DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética Processamento de Proteína Pós-Traducional Proteína SUMO-1/genética Proteínas de Saccharomyces cerevisiae/genética Saccharomyces cerevisiae/metabolismo [Mh] Termos MeSH secundário: Dano ao DNA DNA Fúngico/genética DNA Fúngico/metabolismo DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo Desoxirribonuclease (Dímero de Pirimidina)/genética Desoxirribonuclease (Dímero de Pirimidina)/metabolismo Seres Humanos Peróxido de Hidrogênio/farmacologia Mesilatos/farmacologia Modelos Moleculares Mapeamento de Peptídeos Domínios Proteicos Estrutura Secundária de Proteína Proteínas Recombinantes de Fusão/genética Proteínas Recombinantes de Fusão/metabolismo Proteína SUMO-1/metabolismo Saccharomyces cerevisiae/efeitos dos fármacos Saccharomyces cerevisiae/genética Proteínas de Saccharomyces cerevisiae/metabolismo Sumoilação [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (DNA, Fungal); 0 (Mesylates); 0 (Recombinant Fusion Proteins); 0 (SUMO-1 Protein); 0 (Saccharomyces cerevisiae Proteins); 12EH9M7279 (methanesulfonic acid); BBX060AN9V (Hydrogen Peroxide); EC 3.1.25.1 (Deoxyribonuclease (Pyrimidine Dimer)); EC 3.1.25.1 (NTHL1 protein, human); EC 4.2.99.18 (DNA-(Apurinic or Apyrimidinic Site) Lyase); EC 4.2.99.18 (NTG1 protein, S cerevisiae) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170515 [Lr] Data última revisão: 170515 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161115 [St] Status: MEDLINE

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[PMID]: 27573237 [Au] Autor: Nawaz MS; Vik ES; Berges N; Fladeby C; Bjørås M; Dalhus B; Alseth I [Ad] Endereço: From the Department of Microbiology, Oslo University Hospital HF, Rikshospitalet, and University of Oslo, NO-0424 Oslo. [Ti] Título: Regulation of Human Endonuclease V Activity and Relocalization to Cytoplasmic Stress Granules. [So] Source: J Biol Chem;291(41):21786-21801, 2016 Oct 07. [Is] ISSN: 1083-351X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Endonuclease V (EndoV) is an enzyme with specificity for inosines in nucleic acids. Whereas the bacterial homologs are active on both DNA and RNA, the mammalian variants only cleave RNA, at least when assayed with recombinant proteins. Here we show that ectopically expressed, as well as endogenously expressed human (h)EndoV, share the same enzymatic properties as the recombinant protein and cleaves RNA with inosine but not DNA. In search for proteins interacting with hEndoV, polyadenylate-binding protein C1 (PABPC1) was identified. The association between PABPC1 and hEndoV is RNA dependent and furthermore, PABPC1 stimulates hEndoV activity and affinity for inosine-containing RNA. Upon cellular stress, PABPC1 relocates to cytoplasmic stress granules that are multimolecular aggregates of stalled translation initiation complexes formed to aid cell recovery. Arsenite, as well as other agents, triggered relocalization also of hEndoV to cytoplasmic stress granules. As inosines in RNA are highly abundant, hEndoV activity is likely regulated in cells to avoid aberrant cleavage of inosine-containing transcripts. Indeed, we find that hEndoV cleavage is inhibited by normal intracellular ATP concentrations. The ATP stores inside a cell do not overlay stress granules and we suggest that hEndoV is redistributed to stress granules as a strategy to create a local environment low in ATP to permit hEndoV activity. [Mh] Termos MeSH primário: Trifosfato de Adenosina/metabolismo Grânulos Citoplasmáticos/enzimologia Desoxirribonuclease (Dímero de Pirimidina)/metabolismo RNA/metabolismo [Mh] Termos MeSH secundário: Trifosfato de Adenosina/genética Arsenitos/farmacologia Grânulos Citoplasmáticos/genética Desoxirribonuclease (Dímero de Pirimidina)/genética Células HEK293 Células HeLa Seres Humanos Proteína I de Ligação a Poli(A)/genética Proteína I de Ligação a Poli(A)/metabolismo Transporte Proteico/efeitos dos fármacos Transporte Proteico/fisiologia RNA/genética [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Arsenites); 0 (Poly(A)-Binding Protein I); 63231-63-0 (RNA); 8L70Q75FXE (Adenosine Triphosphate); EC 3.1.25.1 (Deoxyribonuclease (Pyrimidine Dimer)); N5509X556J (arsenite) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 171007 [Lr] Data última revisão: 171007 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160831 [St] Status: MEDLINE

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[PMID]: 26733580 [Au] Autor: Schuermann D; Scheidegger SP; Weber AR; Bjørås M; Leumann CJ; Schär P [Ad] Endereço: Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland david.schuermann@unibas.ch. [Ti] Título: 3CAPS - a structural AP-site analogue as a tool to investigate DNA base excision repair. [So] Source: Nucleic Acids Res;44(5):2187-98, 2016 Mar 18. [Is] ISSN: 1362-4962 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Abasic sites (AP-sites) are frequent DNA lesions, arising by spontaneous base hydrolysis or as intermediates of base excision repair (BER). The hemiacetal at the anomeric centre renders them chemically reactive, which presents a challenge to biochemical and structural investigation. Chemically more stable AP-site analogues have been used to avoid spontaneous decay, but these do not fully recapitulate the features of natural AP-sites. With its 3'-phosphate replaced by methylene, the abasic site analogue 3CAPS was suggested to circumvent some of these limitations. Here, we evaluated the properties of 3CAPS in biochemical BER assays with mammalian proteins. 3CAPS-containing DNA substrates were processed by APE1, albeit with comparably poor efficiency. APE1-cleaved 3CAPS can be extended by DNA polymerase ß but repaired only by strand displacement as the 5'-deoxyribophosphate (dRP) cannot be removed. DNA glycosylases physically and functionally interact with 3CAPS substrates, underlining its structural integrity and biochemical reactivity. The AP lyase activity of bifunctional DNA glycosylases (NTH1, NEIL1, FPG), however, was fully inhibited. Notably, 3CAPS-containing DNA also effectively inhibited the activity of bifunctional glycosylases on authentic substrates. Hence, the chemically stable 3CAPS with its preserved hemiacetal functionality is a potent tool for BER research and a potential inhibitor of bifunctional DNA glycosylases. [Mh] Termos MeSH primário: DNA Polimerase beta/metabolismo Reparo do DNA DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo DNA/química Oligonucleotídeos/química [Mh] Termos MeSH secundário: Acetais/química Acetais/metabolismo Bioensaio Materiais Biomiméticos/química Materiais Biomiméticos/metabolismo Clonagem Molecular DNA/metabolismo Dano ao DNA DNA Glicosilases/genética DNA Glicosilases/metabolismo DNA Polimerase beta/genética DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética Desoxirribonuclease (Dímero de Pirimidina)/genética Desoxirribonuclease (Dímero de Pirimidina)/metabolismo Escherichia coli/genética Escherichia coli/metabolismo Expressão Gênica Seres Humanos Oligonucleotídeos/metabolismo Proteínas Recombinantes/genética Proteínas Recombinantes/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Acetals); 0 (Oligonucleotides); 0 (Recombinant Proteins); 9007-49-2 (DNA); EC 2.7.7.- (DNA Polymerase beta); EC 3.1.25.1 (Deoxyribonuclease (Pyrimidine Dimer)); EC 3.1.25.1 (NTHL1 protein, human); EC 3.2.2.- (DNA Glycosylases); EC 3.2.2.- (NEIL1 protein, human); EC 4.2.99.18 (APEX1 protein, human); EC 4.2.99.18 (DNA-(Apurinic or Apyrimidinic Site) Lyase) [Em] Mês de entrada: 1608 [Cu] Atualização por classe: 160322 [Lr] Data última revisão: 160322 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160107 [St] Status: MEDLINE [do] DOI: 10.1093/nar/gkv1520

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MEDLINE

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[PMID]: 26661446 [Au] Autor: Lee J; Kim Y; Lim S; Jo K [Ad] Endereço: Department of Chemistry and Interdisciplinary Program of Integrated Biotechnology, Sogang University, Seoul, 121-742, Korea. jokyubong@sogang.ac.kr. [Ti] Título: Single-molecule visualization of ROS-induced DNA damage in large DNA molecules. [So] Source: Analyst;141(3):847-52, 2016 Feb 07. [Is] ISSN: 1364-5528 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: We present a single molecule visualization approach for the quantitative analysis of reactive oxygen species (ROS) induced DNA damage, such as base oxidation and single stranded breaks in large DNA molecules. We utilized the Fenton reaction to generate DNA damage with subsequent enzymatic treatment using a mixture of three types of glycosylases to remove oxidized bases, and then fluorescent labeling on damaged lesions via nick translation. This single molecule analytical platform provided the capability to count one or two damaged sites per λ DNA molecule (48.5 kb), which were reliably dependent on the concentrations of hydrogen peroxide and ferrous ion at the micromolar level. More importantly, the labeled damaged sites that were visualized under a microscope provided positional information, which offered the capability of comparing DNA damaged sites with the in silico genomic map to reveal sequence specificity that GTGR is more sensitive to oxidative damage. Consequently, single DNA molecule analysis provides a sensitive analytical platform for ROS-induced DNA damage and suggests an interesting biochemical insight that the genome primarily active during the lysogenic cycle may have less probability for oxidative DNA damage. [Mh] Termos MeSH primário: Dano ao DNA DNA Viral/química Espécies Reativas de Oxigênio/química Imagem Individual de Molécula/métodos [Mh] Termos MeSH secundário: Bacteriófago lambda/genética Benzoxazóis/química Carbocianinas/química Cátions Bivalentes DNA-Formamidopirimidina Glicosilase/química Desoxirribonuclease (Dímero de Pirimidina)/química Desoxirribonucleases de Sítio Específico do Tipo II/química Escherichia coli Proteínas de Escherichia coli/química Peróxido de Hidrogênio/química Ferro/química Microscopia de Fluorescência Compostos de Quinolínio/química [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Alexa Fluor 647); 0 (Benzoxazoles); 0 (Carbocyanines); 0 (Cations, Divalent); 0 (DNA, Viral); 0 (Escherichia coli Proteins); 0 (Quinolinium Compounds); 0 (Reactive Oxygen Species); 143413-85-8 (1,1'-((4,4,7,7-tetramethyl)-4,7-diazaundecamethylene)bis-4-(3-methyl-2,3-dihydro(benzo-1,3-oxazole)-2-methylidene)quinolinium); BBX060AN9V (Hydrogen Peroxide); E1UOL152H7 (Iron); EC 3.1.21.4 (CTCGAG-specific type II deoxyribonucleases); EC 3.1.21.4 (Deoxyribonucleases, Type II Site-Specific); EC 3.1.25.1 (Deoxyribonuclease (Pyrimidine Dimer)); EC 3.1.25.1 (NTH protein, E coli); EC 3.1.25.1 (Nei protein, E coli); EC 3.2.2.23 (DNA-Formamidopyrimidine Glycosylase); EC 3.2.2.23 (DNA-formamidopyrimidine glycosylase, E coli) [Em] Mês de entrada: 1701 [Cu] Atualização por classe: 170131 [Lr] Data última revisão: 170131 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 151215 [St] Status: MEDLINE [do] DOI: 10.1039/c5an01875g

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