Base de dados : MEDLINE
Pesquisa : G02.111.225 [Categoria DeCS]
Referências encontradas : 45683 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 4569 ir para página                         

  1 / 45683 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27770702
[Au] Autor:Mishra P; Dixit U; Pandey AK; Upadhyay A; Pandey VN
[Ad] Endereço:Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, USA.
[Ti] Título:Modulation of HCV replication and translation by ErbB3 binding protein1 isoforms.
[So] Source:Virology;500:35-49, 2017 01.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We recently identified a cell-factor, ErbB3 binding protein 1 (Ebp-1), which specifically interacts with the viral RNA genome and modulates HCV replication and translation. Ebp1 has two isoforms, p48, and p42, that result from differential splicing. We found that both isoforms interact with HCV proteins NS5A and NS5B, as well as cell-factor PKR. The p48 isoform, which localizes in the cytoplasm and nuclei, promoted HCV replication, whereas the shorter p42 isoform, which resides exclusively in the cytoplasm, strongly inhibited HCV replication. Transient expression of individual isoforms in Ebp1-knockdown MH14 cells confirmed that the p48 isoform promotes HCV replication, while the p42 isoform inhibits it. We found that Ebp1-p42 significantly enhanced autophosphorylation of PKR, while Ebp1-p48 isoform strongly inhibited it. We propose that modulation of autophosphorylation of PKR by p48 isoform is an important mechanism whereby the HCV virus escapes innate antiviral immune responses by circumventing p42-mediated inhibition of its replication.
[Mh] Termos MeSH primário: Hepacivirus/fisiologia
Hepatite C/virologia
Replicação Viral
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Replicação do DNA
Hepacivirus/genética
Hepatite C/genética
Hepatite C/metabolismo
Seres Humanos
Queratina-20/genética
Queratina-20/metabolismo
Fosforilação
Biossíntese de Proteínas
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
eIF-2 Quinase/genética
eIF-2 Quinase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (KRT20 protein, human); 0 (Keratin-20); 0 (Protein Isoforms); EC 2.7.11.1 (EIF2AK2 protein, human); EC 2.7.11.1 (eIF-2 Kinase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180303
[Lr] Data última revisão:
180303
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE


  2 / 45683 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29281624
[Au] Autor:Lafuente-Barquero J; Luke-Glaser S; Graf M; Silva S; Gómez-González B; Lockhart A; Lisby M; Aguilera A; Luke B
[Ad] Endereço:Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Avda. Americo Vespucio 24, Seville, Spain.
[Ti] Título:The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage.
[So] Source:PLoS Genet;13(12):e1007136, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RNA-DNA hybrids are naturally occurring obstacles that must be overcome by the DNA replication machinery. In the absence of RNase H enzymes, RNA-DNA hybrids accumulate, resulting in replication stress, DNA damage and compromised genomic integrity. We demonstrate that Mph1, the yeast homolog of Fanconi anemia protein M (FANCM), is required for cell viability in the absence of RNase H enzymes. The integrity of the Mph1 helicase domain is crucial to prevent the accumulation of RNA-DNA hybrids and RNA-DNA hybrid-dependent DNA damage, as determined by Rad52 foci. Mph1 forms foci when RNA-DNA hybrids accumulate, e.g. in RNase H or THO-complex mutants and at short telomeres. Mph1, however is a double-edged sword, whose action at hybrids must be regulated by the Smc5/6 complex. This is underlined by the observation that simultaneous inactivation of RNase H2 and Smc5/6 results in Mph1-dependent synthetic lethality, which is likely due to an accumulation of toxic recombination intermediates. The data presented here support a model, where Mph1's helicase activity plays a crucial role in responding to persistent RNA-DNA hybrids.
[Mh] Termos MeSH primário: Proteínas de Ciclo Celular/genética
RNA Helicases DEAD-box/genética
RNA Helicases DEAD-box/metabolismo
Dano ao DNA
RNA Fúngico/genética
Proteínas de Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Ciclo Celular/metabolismo
DNA/metabolismo
Reparo do DNA
Replicação do DNA/genética
Replicação do DNA/fisiologia
RNA Helicases/metabolismo
RNA Fúngico/metabolismo
Ribonuclease H/genética
Saccharomyces cerevisiae/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (RNA, Fungal); 0 (SMC5 protein, S cerevisiae); 0 (SMC6 protein, S cerevisiae); 0 (Saccharomyces cerevisiae Proteins); 9007-49-2 (DNA); EC 3.1.26.4 (Ribonuclease H); EC 3.6.1.- (MPH1 protein, S cerevisiae); EC 3.6.4.13 (DEAD-box RNA Helicases); EC 3.6.4.13 (RNA Helicases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007136


  3 / 45683 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29281621
[Au] Autor:Tellier-Lebegue C; Dizet E; Ma E; Veaute X; Coïc E; Charbonnier JB; Maloisel L
[Ad] Endereço:I2BC, CEA, CNRS, Univ. Paris-Sud, Univ. Paris-Saclay, Gif-sur-Yvette, France.
[Ti] Título:The translesion DNA polymerases Pol ζ and Rev1 are activated independently of PCNA ubiquitination upon UV radiation in mutants of DNA polymerase δ.
[So] Source:PLoS Genet;13(12):e1007119, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Replicative DNA polymerases cannot insert efficiently nucleotides at sites of base lesions. This function is taken over by specialized translesion DNA synthesis (TLS) polymerases to allow DNA replication completion in the presence of DNA damage. In eukaryotes, Rad6- and Rad18-mediated PCNA ubiquitination at lysine 164 promotes recruitment of TLS polymerases, allowing cells to efficiently cope with DNA damage. However, several studies showed that TLS polymerases can be recruited also in the absence of PCNA ubiquitination. We hypothesized that the stability of the interactions between DNA polymerase δ (Pol δ) subunits and/or between Pol δ and PCNA at the primer/template junction is a crucial factor to determine the requirement of PCNA ubiquitination. To test this hypothesis, we used a structural mutant of Pol δ in which the interaction between Pol3 and Pol31 is inhibited. We found that in yeast, rad18Δ-associated UV hypersensitivity is suppressed by pol3-ct, a mutant allele of the POL3 gene that encodes the catalytic subunit of replicative Pol δ. pol3-ct suppressor effect was specifically dependent on the Rev1 and Pol ζ TLS polymerases. This result strongly suggests that TLS polymerases could rely much less on PCNA ubiquitination when Pol δ interaction with PCNA is partially compromised by mutations. In agreement with this model, we found that the pol3-FI allele suppressed rad18Δ-associated UV sensitivity as observed for pol3-ct. This POL3 allele carries mutations within a putative PCNA Interacting Peptide (PIP) motif. We then provided molecular and genetic evidence that this motif could contribute to Pol δ-PCNA interaction indirectly, although it is not a bona fide PIP. Overall, our results suggest that the primary role of PCNA ubiquitination is to allow TLS polymerases to outcompete Pol δ for PCNA access upon DNA damage.
[Mh] Termos MeSH primário: DNA Polimerase III/metabolismo
[Mh] Termos MeSH secundário: Domínio Catalítico
DNA/genética
DNA/metabolismo
Dano ao DNA
DNA Polimerase III/genética
Reparo do DNA
Replicação do DNA
DNA Polimerase Dirigida por DNA/genética
DNA Polimerase Dirigida por DNA/metabolismo
Modelos Genéticos
Mutação
Nucleotidiltransferases/genética
Nucleotidiltransferases/metabolismo
Antígeno Nuclear de Célula em Proliferação/genética
Antígeno Nuclear de Célula em Proliferação/metabolismo
Ligação Proteica
Saccharomyces cerevisiae
Proteínas de Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/metabolismo
Ubiquitinação
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Proliferating Cell Nuclear Antigen); 0 (Saccharomyces cerevisiae Proteins); 9007-49-2 (DNA); EC 2.7.7.- (DNA Polymerase III); EC 2.7.7.- (DNA polymerase zeta); EC 2.7.7.- (Nucleotidyltransferases); EC 2.7.7.- (REV1 protein, S cerevisiae); EC 2.7.7.7 (DNA-Directed DNA Polymerase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007119


  4 / 45683 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28465355
[Au] Autor:Lan L; Guo M; Ai Y; Chen F; Zhang Y; Xia L; Huang D; Niu L; Zheng Y; Suzuki CK; Zhang Y; Liu Y; Lu B
[Ad] Endereço:Department of Biochemistry, Institute of Biophysics, Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
[Ti] Título:Tetramethylpyrazine blocks TFAM degradation and up-regulates mitochondrial DNA copy number by interacting with TFAM.
[So] Source:Biosci Rep;37(3), 2017 Jun 30.
[Is] ISSN:1573-4935
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The natural small molecule compound: 2,3,5,6-tetramethylpyrazine (TMP), is a major component of the Chinese medicine , which has wide clinical applications in dilating blood vessels, inhibiting platelet aggregation and treating thrombosis. Recent work suggests that TMP is also an antitumour agent. Despite its chemotherapeutic potential, the mechanism(s) underlying TMP action are unknown. Herein, we demonstrate that TMP binds to mitochondrial transcription factor A (TFAM) and blocks its degradation by the mitochondrial Lon protease. TFAM is a key regulator of mtDNA replication, transcription and transmission. Our previous work showed that when TFAM is not bound to DNA, it is rapidly degraded by the ATP-dependent Lon protease, which is essential for mitochondrial proteostasis. In cultured cells, TMP specifically blocks Lon-mediated degradation of TFAM, leading to TFAM accumulation and subsequent up-regulation of mtDNA content in cells with substantially low levels of mtDNA. protease assays show that TMP does not directly inhibit mitochondrial Lon, rather interacts with TFAM and blocks degradation. Pull-down assays show that biotinylated TMP interacts with TFAM. These findings suggest a novel mechanism whereby TMP stabilizes TFAM and confers resistance to Lon-mediated degradation, thereby promoting mtDNA up-regulation in cells with low mtDNA content.
[Mh] Termos MeSH primário: DNA Mitocondrial/efeitos dos fármacos
Proteínas de Ligação a DNA/genética
Dosagem de Genes/efeitos dos fármacos
Mitocôndrias/efeitos dos fármacos
Proteínas Mitocondriais/genética
Pirazinas/farmacologia
Fatores de Transcrição/genética
Regulação para Cima/efeitos dos fármacos
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Replicação do DNA/efeitos dos fármacos
Células HCT116
Células HeLa
Seres Humanos
Peptídeo Hidrolases/genética
Transcrição Genética/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Mitochondrial); 0 (DNA-Binding Proteins); 0 (Mitochondrial Proteins); 0 (Pyrazines); 0 (TFAM protein, human); 0 (Transcription Factors); EC 3.4.- (Peptide Hydrolases); V80F4IA5XG (tetramethylpyrazine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


  5 / 45683 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29288943
[Au] Autor:Qiu J; Gong Q; Gao J; Chen W; Zhang Y; Gu X; Tang D
[Ad] Endereço:Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, People's Republic of China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, People's Republic of China.
[Ti] Título:Design, synthesis and evaluation of novel phenyl propionamide derivatives as non-nucleoside hepatitis B virus inhibitors.
[So] Source:Eur J Med Chem;144:424-434, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:As an ongoing search for potent non-nucleoside anti-HBV agents with novel structures, we described a series of phenyl propionamide derivatives (3a-b, 4a-e, 7a-g, 8a-h and 9a-b) by pharmacophore fusion strategy in the present work. All the compounds exhibited an anti-HBV activity to some extent. Among them, compounds 8d and 9b displayed most potent anti-HBV activity with IC values on HBV DNA replication of 0.46 and 0.14 µM, respectively. And the selective index values of 8d and 9b were more than 217.39 and 153.14, suggesting that 8d and 9b exhibited favorable safety profiles. Interestingly, 8d and 9b possessed significantly antiviral activities against lamivudine and entecavir resistant HBV mutants with IC values of 0.77 and 0.32 µM. Notably, preliminary anti-HBV action mechanism studies showed that 8d could inhibit intracellular HBV pgRNA and RT activity of the HBV polymerase. Molecular docking studies suggested that compound 8d could fit into the dimer-dimer interface of HBV core protein by hydrophobic interaction. In addition, in silico prediction of physicochemical properties showed that 8d conformed well to the Lipinski's rule of five, suggesting its potential for use as a drug like molecule. Taken together, 8d possessed significantly anti-HBV activity, low toxicity, diverse anti-HBV mechanism and favorable physicochemical properties, and warranted further investigation as a promising non-nucleoside anti-HBV candidate.
[Mh] Termos MeSH primário: Amidas/farmacologia
Antivirais/farmacologia
Desenho de Drogas
Vírus da Hepatite B/efeitos dos fármacos
[Mh] Termos MeSH secundário: Amidas/síntese química
Amidas/química
Antivirais/síntese química
Antivirais/química
Sobrevivência Celular/efeitos dos fármacos
Replicação do DNA/efeitos dos fármacos
Relação Dose-Resposta a Droga
Células Hep G2
Seres Humanos
Testes de Sensibilidade Microbiana
Simulação de Acoplamento Molecular
Estrutura Molecular
Relação Estrutura-Atividade
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Antiviral Agents); QK07G0HP47 (propionamide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171231
[St] Status:MEDLINE


  6 / 45683 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29338026
[Au] Autor:Vanzyl EJ; Rick KRC; Blackmore AB; MacFarlane EM; McKay BC
[Ad] Endereço:Department of Biology, Carleton University, Ottawa ON, Canada.
[Ti] Título:Flow cytometric analysis identifies changes in S and M phases as novel cell cycle alterations induced by the splicing inhibitor isoginkgetin.
[So] Source:PLoS One;13(1):e0191178, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The spliceosome is a large ribonucleoprotein complex that catalyzes the removal of introns from RNA polymerase II-transcribed RNAs. Spliceosome assembly occurs in a stepwise manner through specific intermediates referred to as pre-spliceosome complexes E, A, B, B* and C. It has been reported that small molecule inhibitors of the spliceosome that target the SF3B1 protein component of complex A lead to the accumulation of cells in the G1 and G2/M phases of the cell cycle. Here we performed a comprehensive flow cytometry analysis of the effects of isoginkgetin (IGG), a natural compound that interferes with spliceosome assembly at a later step, complex B formation. We found that IGG slowed cell cycle progression in multiple phases of the cell cycle (G1, S and G2) but not M phase. This pattern was somewhat similar to but distinguishable from changes associated with an SF3B1 inhibitor, pladienolide B (PB). Both drugs led to a significant decrease in nascent DNA synthesis in S phase, indicative of an S phase arrest. However, IGG led to a much more prominent S phase arrest than PB while PB exhibited a more pronounced G1 arrest that decreased the proportion of cells in S phase as well. We also found that both drugs led to a comparable decrease in the proportion of cells in M phase. This work indicates that spliceosome inhibitors affect multiple phases of the cell cycle and that some of these effects vary in an agent-specific manner despite the fact that they target splicing at similar stages of spliceosome assembly.
[Mh] Termos MeSH primário: Biflavonoides/farmacologia
Divisão Celular/efeitos dos fármacos
Processamento de RNA/efeitos dos fármacos
Fase S/efeitos dos fármacos
[Mh] Termos MeSH secundário: Ciclo Celular/efeitos dos fármacos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Replicação do DNA/efeitos dos fármacos
Compostos de Epóxi/farmacologia
Citometria de Fluxo
Células HCT116
Seres Humanos
Macrolídeos/farmacologia
Precursores de RNA/metabolismo
Spliceossomos/efeitos dos fármacos
Spliceossomos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biflavonoids); 0 (Epoxy Compounds); 0 (Macrolides); 0 (RNA Precursors); 0 (isoginkgetin); 0 (pladienolide B)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191178


  7 / 45683 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28743715
[Au] Autor:Tak T; Drylewicz J; Conemans L; de Boer RJ; Koenderman L; Borghans JAM; Tesselaar K
[Ad] Endereço:Department of Respiratory Medicine and.
[Ti] Título:Circulatory and maturation kinetics of human monocyte subsets in vivo.
[So] Source:Blood;130(12):1474-1477, 2017 09 21.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Monócitos/citologia
[Mh] Termos MeSH secundário: Asma/sangue
Diferenciação Celular
Senescência Celular
Replicação do DNA
Eosinofilia/sangue
Feminino
Proteínas Ligadas por GPI/análise
Homeostase
Seres Humanos
Imunofenotipagem
Cinética
Contagem de Leucócitos
Receptores de Lipopolissacarídeos/análise
Masculino
Modelos Biológicos
Monócitos/química
Monócitos/classificação
Receptores de IgG/análise
Valores de Referência
[Pt] Tipo de publicação:LETTER; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (FCGR3B protein, human); 0 (GPI-Linked Proteins); 0 (Lipopolysaccharide Receptors); 0 (Receptors, IgG)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2017-03-771261


  8 / 45683 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28450582
[Au] Autor:McConnell MJ; Moran JV; Abyzov A; Akbarian S; Bae T; Cortes-Ciriano I; Erwin JA; Fasching L; Flasch DA; Freed D; Ganz J; Jaffe AE; Kwan KY; Kwon M; Lodato MA; Mills RE; Paquola ACM; Rodin RE; Rosenbluh C; Sestan N; Sherman MA; Shin JH; Song S; Straub RE; Thorpe J; Weinberger DR; Urban AE; Zhou B; Gage FH; Lehner T; Senthil G; Walsh CA; Chess A; Courchesne E; Gleeson JG; Kidd JM; Park PJ; Pevsner J; Vaccarino FM; Brain Somatic Mosaicism Network
[Ti] Título:Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network.
[So] Source:Science;356(6336), 2017 Apr 28.
[Is] ISSN:1095-9203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Neuropsychiatric disorders have a complex genetic architecture. Human genetic population-based studies have identified numerous heritable sequence and structural genomic variants associated with susceptibility to neuropsychiatric disease. However, these germline variants do not fully account for disease risk. During brain development, progenitor cells undergo billions of cell divisions to generate the ~80 billion neurons in the brain. The failure to accurately repair DNA damage arising during replication, transcription, and cellular metabolism amid this dramatic cellular expansion can lead to somatic mutations. Somatic mutations that alter subsets of neuronal transcriptomes and proteomes can, in turn, affect cell proliferation and survival and lead to neurodevelopmental disorders. The long life span of individual neurons and the direct relationship between neural circuits and behavior suggest that somatic mutations in small populations of neurons can significantly affect individual neurodevelopment. The Brain Somatic Mosaicism Network has been founded to study somatic mosaicism both in neurotypical human brains and in the context of complex neuropsychiatric disorders.
[Mh] Termos MeSH primário: Encéfalo/anormalidades
Transtornos Mentais/genética
Mosaicismo
Doenças do Sistema Nervoso/genética
Células-Tronco Neurais/fisiologia
Neurônios/fisiologia
[Mh] Termos MeSH secundário: Encéfalo/metabolismo
Divisão Celular/genética
Dano ao DNA
Análise Mutacional de DNA/métodos
Reparo do DNA/genética
Replicação do DNA
Genoma Humano
Células Germinativas/metabolismo
Seres Humanos
Rede Nervosa/crescimento & desenvolvimento
Rede Nervosa/metabolismo
Células-Tronco Neurais/metabolismo
Neurônios/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


  9 / 45683 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29371596
[Au] Autor:Duch A; Canal B; Barroso SI; García-Rubio M; Seisenbacher G; Aguilera A; de Nadal E; Posas F
[Ad] Endereço:Cell Signaling Research Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra (UPF), E-08003, Barcelona, Spain.
[Ti] Título:Multiple signaling kinases target Mrc1 to prevent genomic instability triggered by transcription-replication conflicts.
[So] Source:Nat Commun;9(1):379, 2018 01 25.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Conflicts between replication and transcription machineries represent a major source of genomic instability and cells have evolved strategies to prevent such conflicts. However, little is known regarding how cells cope with sudden increases of transcription while replicating. Here, we report the existence of a general mechanism for the protection of genomic integrity upon transcriptional outbursts in S phase that is mediated by Mrc1. The N-terminal phosphorylation of Mrc1 blocked replication and prevented transcription-associated recombination (TAR) and genomic instability during stress-induced gene expression in S phase. An unbiased kinome screening identified several kinases that phosphorylate Mrc1 at the N terminus upon different environmental stresses. Mrc1 function was not restricted to environmental cues but was also required when unscheduled transcription was triggered by low fitness states such as genomic instability or slow growth. Our data indicate that Mrc1 integrates multiple signals, thereby defining a general safeguard mechanism to protect genomic integrity upon transcriptional outbursts.
[Mh] Termos MeSH primário: Proteínas de Ciclo Celular/genética
Replicação do DNA
Regulação Fúngica da Expressão Gênica
Instabilidade Genômica
Proteínas Serina-Treonina Quinases/genética
Proteínas de Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/genética
Transcrição Genética
[Mh] Termos MeSH secundário: Proteínas de Ciclo Celular/metabolismo
Escherichia coli/genética
Escherichia coli/metabolismo
Glucose/deficiência
Temperatura Alta
Peróxido de Hidrogênio/farmacologia
Pressão Osmótica
Estresse Oxidativo/genética
Fosforilação
Proteínas Serina-Treonina Quinases/metabolismo
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Fase S
Saccharomyces cerevisiae/efeitos dos fármacos
Saccharomyces cerevisiae/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
Transdução de Sinais
Cloreto de Sódio/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (MRC1 protein, S cerevisiae); 0 (Recombinant Proteins); 0 (Saccharomyces cerevisiae Proteins); 451W47IQ8X (Sodium Chloride); BBX060AN9V (Hydrogen Peroxide); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02756-x


  10 / 45683 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28467906
[Au] Autor:Muñoz S; Búa S; Rodríguez-Acebes S; Megías D; Ortega S; de Martino A; Méndez J
[Ad] Endereço:DNA Replication Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 3 Melchor Fernández Almagro, 28029 Madrid, Spain.
[Ti] Título:In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias.
[So] Source:Cell Rep;19(5):928-938, 2017 May 02.
[Is] ISSN:2211-1247
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mammalian DNA replication origins are "licensed" by the loading of DNA helicases, a reaction that is mediated by CDC6 and CDT1 proteins. After initiation of DNA synthesis, CDC6 and CDT1 are inhibited to prevent origin reactivation and DNA overreplication before cell division. CDC6 and CDT1 are highly expressed in many types of cancer cells, but the impact of their deregulated expression had not been investigated in vivo. Here, we have generated mice strains that allow the conditional overexpression of both proteins. Adult mice were unharmed by the individual overexpression of either CDC6 or CDT1, but their combined deregulation led to DNA re-replication in progenitor cells and lethal tissue dysplasias. This study offers mechanistic insights into the necessary cooperation between CDC6 and CDT1 for facilitation of origin reactivation and describes the physiological consequences of DNA overreplication.
[Mh] Termos MeSH primário: Replicação do DNA
Diarreia Infantil/genética
Mucosa Intestinal/metabolismo
Síndromes de Malabsorção/genética
[Mh] Termos MeSH secundário: Animais
Proteínas de Ciclo Celular/genética
Proteínas de Ciclo Celular/metabolismo
Proteínas de Ligação a DNA/genética
Proteínas de Ligação a DNA/metabolismo
Diarreia Infantil/metabolismo
Feminino
Mucosa Intestinal/patologia
Síndromes de Malabsorção/metabolismo
Masculino
Camundongos
Proteínas Nucleares/genética
Proteínas Nucleares/metabolismo
Transgenes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CDC6 protein, mouse); 0 (Cell Cycle Proteins); 0 (DNA-Binding Proteins); 0 (Nuclear Proteins); 0 (Ris2 protein, mouse)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE



página 1 de 4569 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde