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[PMID]:29242886
[Au] Autor:Romero EE; Hernandez FE
[Ad] Endereço:Department of Chemistry, University of Central Florida, P. O. Box 162366, Orlando, Florida 32816-2366, USA. florencio.hernandez@ucf.edu.
[Ti] Título:Solvent effect on the intermolecular proton transfer of the Watson and Crick guanine-cytosine and adenine-thymine base pairs: a polarizable continuum model study.
[So] Source:Phys Chem Chem Phys;20(2):1198-1209, 2018 Jan 03.
[Is] ISSN:1463-9084
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Herein we present our results on the study of the double proton transfer (DPT) mechanism in the adenine-thymine (AT) and guanine-cytosine (GC) base pairs, both in gas phase and in solution. The latter was modeled using the polarizable continuum method (PCM) in different solvents. According to our DFT calculations, the DPT may occur for both complexes in a stepwise mechanism in condensate phase. In gas phase only the GC base pair exhibits a concerted DPT mechanism. Using the Wigner's tunneling corrections to the transition state theory we demonstrate that such corrections are important for the prediction of the rate constants of both systems in gas and in condensate phase. We also show that (i) as the polarity of the medium decreases the equilibrium constant of the DPT reaction increases in both complexes, and (ii) that the equilibrium constant in the GC complex is four orders of magnitude larger than in AT. This observation suggests that the spontaneous mutations in DNA base pairs are more probable in GC than in AT.
[Mh] Termos MeSH primário: Pareamento de Bases
DNA/química
Modelos Moleculares
[Mh] Termos MeSH secundário: Adenina
Citosina
Guanina
Prótons
Solventes
Timina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protons); 0 (Solvents); 5Z93L87A1R (Guanine); 8J337D1HZY (Cytosine); 9007-49-2 (DNA); JAC85A2161 (Adenine); QR26YLT7LT (Thymine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1039/c7cp05356h


  2 / 5895 MEDLINE  
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[PMID]:29190698
[Au] Autor:Foksinski M; Zarakowska E; Gackowski D; Skonieczna M; Gajda K; Hudy D; Szpila A; Bialkowski K; Starczak M; Labejszo A; Czyz J; Rzeszowska-Wolny J; Olinski R
[Ad] Endereço:Department of Clinical Biochemistry, Faculty of Pharmacy, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
[Ti] Título:Profiles of a broad spectrum of epigenetic DNA modifications in normal and malignant human cell lines: Proliferation rate is not the major factor responsible for the 5-hydroxymethyl-2'-deoxycytidine level in cultured cancerous cell lines.
[So] Source:PLoS One;12(11):e0188856, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Active demethylation of 5-methylcytosine moiety in DNA occurs by its sequential oxidation to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine, catalysed by enzymes of the Ten-Eleven Translocation family proteins (TETs 1, 2 and 3). Here we analyzed for the first time all the intermediate products of DNA demethylation pathway in the form of deoxynucleosides (5-methyl-2'-deoxycytidine, 5-(hydroxymethyl)-2'-deoxycytidine, 5-formyl-2'-deoxycytidine and 5-carboxy-2'-deoxycytidine as well as 5-(hydroxymethyl)-2'-deoxyuridine) using automated isotope-dilution online two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry. DNA was isolated from human malignant cell lines of colon adenocarcinoma (HCT 116), melanoma (Me45), myelogenous leukemia bone marrow blasts (K562), EBV-positive Burkitt's lymphoma lymphoblasts (Raji), EBV-negative Burkitt's lymphoma lymphoblasts (male-CA46 and female-ST486), as well as normal neonatal dermal fibroblasts (NHDF-Neo). The expression levels of TET1, TET2, TET3, SMUG1, and TDG genes were also assayed by RT-qPCR. Our results show a global erasure of 5-hydroxymethyl-2'-deoxycytidine and 5-carboxy-2'-deoxycytidine in DNA of cultured cells compared with DNA from primary malignant tissue. Moreover, malignant cells in culture have a quite different DNA epigenetic profile than cultured normal cells, and different types of malignant cells display different and characteristic profiles of DNA epigenetic marks. Similar analyses of a broader spectrum of epigenetic modifications, not restricted to 5-methyl-2'-deoxycytidine, could lead to better understanding of the mechanism(s) responsible for emergence of different types of cancer cells.
[Mh] Termos MeSH primário: Proliferação Celular/efeitos dos fármacos
DNA/genética
Desoxicitidina/análogos & derivados
Epigênese Genética
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Cromatografia Líquida
Citosina/análise
DNA/química
Desoxicitidina/farmacologia
Seres Humanos
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Espectrometria de Massas em Tandem
Timina/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5-hydroxymethyl-2'-deoxycytidine); 0W860991D6 (Deoxycytidine); 8J337D1HZY (Cytosine); 9007-49-2 (DNA); QR26YLT7LT (Thymine)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188856


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[PMID]:28817834
[Au] Autor:Chen Y; Wang DD; Wu YP; Su D; Zhou TY; Gai RH; Fu YY; Zheng L; He QJ; Zhu H; Yang B
[Ad] Endereço:Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology &Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
[Ti] Título:MDM2 promotes epithelial-mesenchymal transition and metastasis of ovarian cancer SKOV3 cells.
[So] Source:Br J Cancer;117(8):1192-1201, 2017 Oct 10.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Metastasis accounts for the most lethal reason for the death of ovarian cancer patients, but remains largely untreated. Epithelial-mesenchymal transition (EMT) is critical for the conversion of early-stage ovarian tumours into metastatic malignancies. Thus the exploration of the signalling pathways promoting EMT would open potential opportunities for the treatment of metastatic ovarian cancer. Herein, the putative role of MDM2 in regulating EMT and metastasis of ovarian cancer SKOV3 cells was investigated. METHODS: The regulatory effects by MDM2 on cell motility was emulated by wound-healing and transwell assays. The effects on EMT transition and Smad pathway were studied by depicting the expression levels of epithelial marker E-cadherin as well as key components of Smad pathway. To evaluate the clinical relevance of our findings, the correlation of MDM2 expression levels with the stages of 104 ovarian cancer patients was investigated by immunohistochemistry assay. RESULTS: We demonstrate that MDM2 functions as a key factor to drive EMT and motility of ovarian SKOV3 cells, by facilitating the activation of TGF-ß-Smad pathway, which results in the increased transcription of snail/slug and the subsequent loss of E-cadherin levels. Such induction of EMT is sustained in either E3 ligase-depleted MDM2 or E3 ligase inhibitor HLI-373-treated cells, while being impaired by the N-terminal deletion of MDM2, which is also reflected by the inhibitory effects against EMT by Nutlin-3a, the N-terminal targeting agent. The expression levels of MDM2 is highly correlated with the stages of the ovarian cancer patients, and the higher expression of MDM2 together with TGFB are closely correlated with poor prognosis and predict a high risk of ovarian cancer patients. CONCLUSIONS: This study suggests that MDM2 activates Smad pathway to promote EMT in ovarian cancer metastasis, and targeting the N-terminal of MDM2 can reprogram EMT and impede the mobility of cancer cells.
[Mh] Termos MeSH primário: Carcinoma/genética
Transição Epitelial-Mesenquimal/genética
Neoplasias Ovarianas/genética
Proteínas Proto-Oncogênicas c-mdm2/genética
[Mh] Termos MeSH secundário: Aminoquinolinas/farmacologia
Western Blotting
Caderinas/metabolismo
Carcinoma/metabolismo
Carcinoma/patologia
Linhagem Celular Tumoral
Movimento Celular/genética
Transição Epitelial-Mesenquimal/efeitos dos fármacos
Feminino
Imunofluorescência
Técnicas de Silenciamento de Genes
Seres Humanos
Imuno-Histoquímica
Metástase Neoplásica
Estadiamento de Neoplasias
Neoplasias Ovarianas/metabolismo
Neoplasias Ovarianas/patologia
Proteínas Proto-Oncogênicas c-mdm2/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-mdm2/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Transdução de Sinais
Proteínas Smad/metabolismo
Fatores de Transcrição da Família Snail/genética
Timina/análogos & derivados
Timina/farmacologia
Fator de Crescimento Transformador beta/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5-(3-dimethylaminopropylamino)-3,10-dimethyl-10H-pyrimido(4,5-b)quinoline-2,4-dione); 0 (Aminoquinolines); 0 (CDH1 protein, human); 0 (Cadherins); 0 (SNAI1 protein, human); 0 (Smad Proteins); 0 (Snail Family Transcription Factors); 0 (Transforming Growth Factor beta); EC 2.3.2.27 (MDM2 protein, human); EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2); QR26YLT7LT (Thymine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.265


  4 / 5895 MEDLINE  
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[PMID]:28720682
[Au] Autor:Do H; Molania R; Mitchell PL; Vaiskunaite R; Murdoch JD; Dobrovic A
[Ad] Endereço:Translational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, Australia; Hongdo.Do@onjcri.org.au Alex.Dobrovic@onjcri.org.au.
[Ti] Título:Reducing Artifactual T790M Mutations in DNA from Formalin-Fixed Paraffin-Embedded Tissue by Use of Thymine-DNA Glycosylase.
[So] Source:Clin Chem;63(9):1506-1514, 2017 Sep.
[Is] ISSN:1530-8561
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: False-positive T790M mutations have been reported in formalin-fixed lung tumors, but the cause of the false positives has not been identified. The T790M mutation results from a C>T change at the cytosine of a CpG dinucleotide. The presence or absence of methylation at this cytosine has different consequences following deamination, resulting in a thymine or uracil, respectively, both of which however result in an artifactual change. Uracil-DNA glycosylase (UDG) can be used to eliminate DNA templates with uracil residues but is not active against artifactual thymines. We therefore investigated the use of thymine-DNA glycosylase (TDG) to reduce artifactual T790M mutations. METHODS: Formalin-fixed normal lung tissues and lung squamous cell carcinomas were tested to measure the frequency of false-positive mutations by use of droplet digital PCR before and after treatment with either UDG or TDG. Methylation at the cytosine at T790 was assessed by pyrosequencing and by analysis of public databases. RESULTS: Artifactual T790M mutations were detected in all of the archival formalin-fixed normal lung and lung squamous cell carcinomas at mutant allele frequencies of 1% or lower. The cytosine at T790 showed high levels of methylation in all lung cancer samples and normal tissues. Pretreatment of the formalin-fixed DNA with either UDG or TDG reduced the false T790M mutations, but a greater reduction was seen with the TDG treatment. CONCLUSIONS: Both U:G and T:G lesions in formalin-fixed tissue are sources of false-positive T790M mutations. This is the first report of the use of TDG to reduce sequence artifacts in formalin-fixed DNA and is applicable to the accurate detection of mutations arising at methylated cytosines.
[Mh] Termos MeSH primário: DNA Glicosilases/metabolismo
Erros de Diagnóstico/prevenção & controle
Genes erbB-1/genética
Técnicas de Diagnóstico Molecular/métodos
Mutação/genética
Inclusão em Parafina
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Reações Falso-Positivas
Seres Humanos
Técnicas de Diagnóstico Molecular/normas
Neoplasias/diagnóstico
Neoplasias/genética
Timina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.2.2.- (DNA Glycosylases); QR26YLT7LT (Thymine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170720
[St] Status:MEDLINE
[do] DOI:10.1373/clinchem.2017.271932


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[PMID]:28575445
[Au] Autor:Melikishvili M; Fried MG
[Ad] Endereço:Center for Structural Biology, Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.
[Ti] Título:Quaternary interactions and supercoiling modulate the cooperative DNA binding of AGT.
[So] Source:Nucleic Acids Res;45(12):7226-7236, 2017 Jul 07.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Human O6-alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O6-alkylguanine and O4-alkylthymine adducts in single-stranded and duplex DNAs. The search for these lesions, through a vast excess of competing, unmodified genomic DNA, is a mechanistic challenge that may limit the repair rate in vivo. Here, we examine influences of DNA secondary structure and twist on protein-protein interactions in cooperative AGT complexes formed on lesion-free DNAs that model the unmodified parts of the genome. We used a new approach to resolve nearest neighbor (nn) and long-range (lr) components from the ensemble-average cooperativity, ωave. We found that while nearest-neighbor contacts were significant, long-range interactions dominated cooperativity and this pattern held true whether the DNA was single-stranded or duplex. Experiments with single plasmid topoisomers showed that the average cooperativity was sensitive to DNA twist, and was strongest when the DNA was slightly underwound. This suggests that AGT proteins are optimally juxtaposed when the DNA is near its torsionally-relaxed state. Most striking was the decline of binding stoichiometry with linking number. As stoichiometry and affinity differences were not correlated, we interpret this as evidence that supercoiling occludes AGT binding sites. These features suggest that AGT's lesion-search distributes preferentially to sites containing torsionally-relaxed DNA, in vivo.
[Mh] Termos MeSH primário: Reparo do DNA
DNA/química
Guanina/análogos & derivados
O(6)-Metilguanina-DNA Metiltransferase/química
Timina/análogos & derivados
[Mh] Termos MeSH secundário: Sítios de Ligação
Clonagem Molecular
DNA/metabolismo
DNA Topoisomerases Tipo I/química
DNA Topoisomerases Tipo I/metabolismo
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Guanina/metabolismo
Seres Humanos
Cinética
Modelos Moleculares
Mutação
O(6)-Metilguanina-DNA Metiltransferase/genética
O(6)-Metilguanina-DNA Metiltransferase/metabolismo
Ligação Proteica
Conformação Proteica em alfa-Hélice
Domínios e Motivos de Interação entre Proteínas
Estrutura Quaternária de Proteína
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Especificidade por Substrato
Termodinâmica
Timina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Recombinant Proteins); 5Z93L87A1R (Guanine); 9007-49-2 (DNA); EC 2.1.1.63 (O(6)-Methylguanine-DNA Methyltransferase); EC 5.99.1.2 (DNA Topoisomerases, Type I); QR26YLT7LT (Thymine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx223


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[PMID]:28525579
[Au] Autor:Wang K; Taylor JA
[Ad] Endereço:Department of Chemistry, Washington University, St Louis, MO 63130, USA.
[Ti] Título:Modulation of cyclobutane thymine photodimer formation in T11-tracts in rotationally phased nucleosome core particles and DNA minicircles.
[So] Source:Nucleic Acids Res;45(12):7031-7041, 2017 Jul 07.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cyclobutane pyrimidine dimers (CPDs) are DNA photoproducts linked to skin cancer, whose mutagenicity depends in part on their frequency of formation and deamination. Nucleosomes modulate CPD formation, favoring outside facing sites and disfavoring inward facing sites. A similar pattern of CPD formation in protein-free DNA loops suggests that DNA bending causes the modulation in nucleosomes. To systematically study the cause and effect of nucleosome structure on CPD formation and deamination, we have developed a circular permutation synthesis strategy for positioning a target sequence at different superhelix locations (SHLs) across a nucleosome in which the DNA has been rotationally phased with respect to the histone octamer by TG motifs. We have used this system to show that the nucleosome dramatically modulates CPD formation in a T11-tract that covers one full turn of the nucleosome helix at seven different SHLs, and that the position of maximum CPD formation at all locations is shifted to the 5΄-side of that found in mixed-sequence nucleosomes. We also show that an 80-mer minicircle DNA using the same TG-motifs faithfully reproduces the CPD pattern in the nucleosome, indicating that it is a good model for protein-free rotationally phased bent DNA of the same curvature as in a nucleosome, and that bending is modulating CPD formation.
[Mh] Termos MeSH primário: DNA Circular/química
Histonas/química
Nucleossomos/efeitos da radiação
Dímeros de Pirimidina/agonistas
Timina/química
[Mh] Termos MeSH secundário: Animais
Galinhas
DNA Circular/isolamento & purificação
Desaminação
Eritrócitos/química
Histonas/metabolismo
Seres Humanos
Mutagênese
Conformação de Ácido Nucleico
Nucleossomos/química
Nucleossomos/metabolismo
Dímeros de Pirimidina/química
Dímeros de Pirimidina/metabolismo
Timina/metabolismo
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Circular); 0 (Histones); 0 (Nucleosomes); 0 (Pyrimidine Dimers); QR26YLT7LT (Thymine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx427


  7 / 5895 MEDLINE  
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[PMID]:28362220
[Au] Autor:Elgemeie GH; Farag AB
[Ad] Endereço:a Chemistry Department, Faculty of Science , Helwan University , Helwan , Cairo , Egypt.
[Ti] Título:Design, synthesis, and in vitro anti-hepatocellular carcinoma of novel thymine thioglycoside analogs as new antimetabolic agents.
[So] Source:Nucleosides Nucleotides Nucleic Acids;36(5):328-342, 2017 May 04.
[Is] ISSN:1532-2335
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A first reported direct method for preparation of thymine thioglycoside analogs utilizing novel pyrimidine-2(1H)-thiones and α-bromoglucose or α-bromogalactose tetraacetate as starting components is described. The synthetic potential of the method is demonstrated. The evaluation of antiproliferative activity against HepG-2 cell lines (Liver carcinoma cell lines) shows that most of the compounds have high antitumor activities especially 6b, 6e, 11b, and 12b. Moreover, molecular modelings of these compounds reveal that they have high binding affinity through hydrogen bond interaction with the binding pocket of thymidylate synthase dihydrofolate reductase (TS-DHFR).
[Mh] Termos MeSH primário: Antineoplásicos/química
Antineoplásicos/farmacologia
Carcinoma Hepatocelular/tratamento farmacológico
Desenho de Drogas
Neoplasias Hepáticas/tratamento farmacológico
Tioglicosídeos/química
Tioglicosídeos/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Carcinoma Hepatocelular/metabolismo
Proliferação Celular/efeitos dos fármacos
Ensaios de Seleção de Medicamentos Antitumorais
Células Hep G2
Seres Humanos
Fígado/efeitos dos fármacos
Fígado/metabolismo
Neoplasias Hepáticas/metabolismo
Modelos Moleculares
Complexos Multienzimáticos/metabolismo
Tetra-Hidrofolato Desidrogenase/metabolismo
Tioglicosídeos/síntese química
Timidilato Sintase/metabolismo
Timina/análogos & derivados
Timina/síntese química
Timina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Multienzyme Complexes); 0 (Thioglycosides); 0 (thymidylate synthase-dihydrofolate reductase); EC 1.5.1.3 (Tetrahydrofolate Dehydrogenase); EC 2.1.1.45 (Thymidylate Synthase); QR26YLT7LT (Thymine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170401
[St] Status:MEDLINE
[do] DOI:10.1080/15257770.2017.1287377


  8 / 5895 MEDLINE  
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[PMID]:28320593
[Au] Autor:Yang L; Jian Y; Setlow P; Li L
[Ad] Endereço:Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis (IUPUI), 402 North Blackford Street, Indianapolis, IN 46202, United States.
[Ti] Título:Spore photoproduct within DNA is a surprisingly poor substrate for its designated repair enzyme-The spore photoproduct lyase.
[So] Source:DNA Repair (Amst);53:31-42, 2017 May.
[Is] ISSN:1568-7856
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:DNA repair enzymes typically recognize their substrate lesions with high affinity to ensure efficient lesion repair. In UV irradiated endospores, a special thymine dimer, 5-thyminyl-5,6-dihydrothymine, termed the spore photoproduct (SP), is the dominant DNA photolesion, which is rapidly repaired during spore outgrowth mainly by spore photoproduct lyase (SPL) using an unprecedented protein-harbored radical transfer process. Surprisingly, our in vitro studies using SP-containing short oligonucleotides, pUC 18 plasmid DNA, and E. coli genomic DNA found that they are all poor substrates for SPL in general, exhibiting turnover numbers of 0.01-0.2min . The faster turnover numbers are reached under single turnover conditions, and SPL activity is low with oligonucleotide substrates at higher concentrations. Moreover, SP-containing oligonucleotides do not go past one turnover. In contrast, the dinucleotide SP TpT exhibits a turnover number of 0.3-0.4min , and the reaction may reach up to 10 turnovers. These observations distinguish SPL from other specialized DNA repair enzymes. To the best of our knowledge, SPL represents an unprecedented example of a major DNA repair enzyme that cannot effectively repair its substrate lesion within the normal DNA conformation adopted in growing cells. Factors such as other DNA binding proteins, helicases or an altered DNA conformation may cooperate with SPL to enable efficient SP repair in germinating spores. Therefore, both SP formation and SP repair are likely to be tightly controlled by the unique cellular environment in dormant and outgrowing spore-forming bacteria, and thus SP repair may be extremely slow in non-spore-forming organisms.
[Mh] Termos MeSH primário: Bacillus subtilis/enzimologia
Reparo do DNA
DNA Bacteriano/metabolismo
Desoxirribodipirimidina Fotoliase/metabolismo
Timina/análogos & derivados
[Mh] Termos MeSH secundário: Bacillus subtilis/genética
Proteínas de Bactérias/metabolismo
Dano ao DNA
DNA Bacteriano/efeitos da radiação
Escherichia coli/metabolismo
Cinética
Dímeros de Pirimidina/metabolismo
Timina/metabolismo
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (DNA, Bacterial); 0 (Pyrimidine Dimers); 28100-77-8 (5-thyminyl-5,6-dihydrothymine); EC 4.1.99.3 (Deoxyribodipyrimidine Photo-Lyase); QR26YLT7LT (Thymine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE


  9 / 5895 MEDLINE  
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[PMID]:28158710
[Au] Autor:Hong S; Wang D; Horton JR; Zhang X; Speck SH; Blumenthal RM; Cheng X
[Ad] Endereço:Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA.
[Ti] Título:Methyl-dependent and spatial-specific DNA recognition by the orthologous transcription factors human AP-1 and Epstein-Barr virus Zta.
[So] Source:Nucleic Acids Res;45(5):2503-2515, 2017 Mar 17.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:T: Activator protein 1 (AP-1) is a transcription factor that recognizes two versions of a 7-base pair response element, either 5΄- GAG CA-3΄ or 5΄- GAG CA-3΄ (where M = 5-methylcytosine). These two elements share the feature that 5-methylcytosine and thymine both have a methyl group in the same position, 5-carbon of the pyrimidine, so each of them has two methyl groups at nucleotide positions 1 and 5 from the 5΄ end, resulting in four methyl groups symmetrically positioned in duplex DNA. Epstein-Barr Virus Zta is a key transcriptional regulator of the viral lytic cycle that is homologous to AP-1. Zta recognizes several methylated Zta-response elements, including meZRE1 (5΄- GAG C A-3΄) and meZRE2 (5΄- GAG G A-3΄), where a methylated cytosine occupies one of the inner thymine residues corresponding to the AP-1 element, resulting in the four spatially equivalent methyl groups. Here, we study how AP-1 and Zta recognize these methyl groups within their cognate response elements. These methyl groups are in van der Waals contact with a conserved di-alanine in AP-1 dimer (Ala265 and Ala266 in Jun), or with the corresponding Zta residues Ala185 and Ser186 (via its side chain carbon Cß atom). Furthermore, the two ZRE elements differ at base pair 6 (C:G versus G:C), forming a pseudo-symmetric sequence (meZRE1) or an asymmetric sequence (meZRE2). In vitro DNA binding assays suggest that Zta has high affinity for all four sequences examined, whereas AP-1 has considerably reduced affinity for the asymmetric sequence (meZRE2). We ascribe this difference to Zta Ser186 (a unique residue for Zta) whose side chain hydroxyl oxygen atom interacts with the two half sites differently, whereas the corresponding Ala266 of AP-1 Jun protein lacks such flexibility. Our analyses demonstrate a novel mechanism of 5mC/T recognition in a methylation-dependent, spatial and sequence-specific approach by basic leucine-zipper transcriptional factors.
[Mh] Termos MeSH primário: Metilação de DNA
Proteínas Proto-Oncogênicas c-jun/química
Elementos de Resposta
Transativadores/química
[Mh] Termos MeSH secundário: 5-Metilcitosina/química
Pareamento de Bases
Sítios de Ligação
DNA/química
DNA/metabolismo
Seres Humanos
Ligação Proteica
Multimerização Proteica
Proteínas Proto-Oncogênicas c-jun/metabolismo
Timina/química
Transativadores/metabolismo
Fator de Transcrição AP-1/química
Fator de Transcrição AP-1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BZLF1 protein, Herpesvirus 4, Human); 0 (Proto-Oncogene Proteins c-jun); 0 (Trans-Activators); 0 (Transcription Factor AP-1); 6R795CQT4H (5-Methylcytosine); 9007-49-2 (DNA); QR26YLT7LT (Thymine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170204
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx057


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[PMID]:28106332
[Au] Autor:Kotera N; Guillot R; Teulade-Fichou MP; Granzhan A
[Ad] Endereço:CNRS UMR9187, INSERM U1196, Institut Curie, PSL Research University, 91405, Orsay, France.
[Ti] Título:Copper(II)-Controlled Molecular Glue for Mismatched DNA.
[So] Source:Chembiochem;18(7):618-622, 2017 Apr 04.
[Is] ISSN:1439-7633
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Isothermal hybridization of two DNA strands bearing three thymine-thymine (T:T) mismatches can be brought about in the presence of a stoichiometric amount of a bis-naphthalene macrocycle, 2,7-BisNP-NH. This process can be reverted by addition of a Cu salt due to formation of a dinuclear metal complex which does not bind to DNA. Subsequent sequestration of Cu releases the macrocycle and restores the hybridization state of DNA strands, thus allowing implementation of a fast fluorescent two-state DNA switch.
[Mh] Termos MeSH primário: Complexos de Coordenação/química
Cobre/química
DNA/química
Substâncias Intercalantes/química
Compostos Macrocíclicos/química
Naftalenos/química
Percloratos/química
[Mh] Termos MeSH secundário: Pareamento Incorreto de Bases
Ácido Edético/química
Ligantes
Desnaturação de Ácido Nucleico
Hibridização de Ácido Nucleico
Temperatura Ambiente
Timina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coordination Complexes); 0 (Intercalating Agents); 0 (Ligands); 0 (Macrocyclic Compounds); 0 (Naphthalenes); 0 (Perchlorates); 13770-18-8 (copper(II) perchlorate); 789U1901C5 (Copper); 9007-49-2 (DNA); 9G34HU7RV0 (Edetic Acid); QR26YLT7LT (Thymine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170121
[St] Status:MEDLINE
[do] DOI:10.1002/cbic.201600675



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