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Pesquisa : D08.811.277.040.025.159 [Categoria DeCS]
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[PMID]:29295984
[Au] Autor:Goyal N; Rossi MJ; Mazina OM; Chi Y; Moritz RL; Clurman BE; Mazin AV
[Ad] Endereço:Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA.
[Ti] Título:RAD54 N-terminal domain is a DNA sensor that couples ATP hydrolysis with branch migration of Holliday junctions.
[So] Source:Nat Commun;9(1):34, 2018 01 02.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In eukaryotes, RAD54 catalyzes branch migration (BM) of Holliday junctions, a basic process during DNA repair, replication, and recombination. RAD54 also stimulates RAD51 recombinase and has other activities. Here, we investigate the structural determinants for different RAD54 activities. We find that the RAD54 N-terminal domain (NTD) is responsible for initiation of BM through two coupled, but distinct steps; specific binding to Holliday junctions and RAD54 oligomerization. Furthermore, we find that the RAD54 oligomeric state can be controlled by NTD phosphorylation at S49, a CDK2 consensus site, which inhibits RAD54 oligomerization and, consequently, BM. Importantly, the effect of phosphorylation on RAD54 oligomerization is specific for BM, as it does not affect stimulation of RAD51 recombinase by RAD54. Thus, the transition of the oligomeric states provides an important control of the biological functions of RAD54 and, likely, other multifunctional proteins.
[Mh] Termos MeSH primário: Adenosina Trifosfatases/metabolismo
DNA Helicases/metabolismo
DNA Cruciforme/metabolismo
Proteínas Nucleares/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sítios de Ligação/genética
Linhagem Celular
DNA Helicases/química
DNA Helicases/genética
Reparo do DNA
DNA Cruciforme/química
DNA Cruciforme/genética
Seres Humanos
Hidrólise
Proteínas Nucleares/química
Proteínas Nucleares/genética
Conformação de Ácido Nucleico
Fosforilação
Multimerização Proteica
Recombinação Genética
Homologia de Sequência de Aminoácidos
Células Sf9
Spodoptera
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (DNA, Cruciform); 0 (Nuclear Proteins); 0 (RAD54L protein, human); EC 3.6.1.- (Adenosine Triphosphatases); EC 3.6.4.- (DNA Helicases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02497-x


  2 / 10382 MEDLINE  
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[PMID]:29371594
[Au] Autor:Rhee S; Chung JI; King DA; D'amato G; Paik DT; Duan A; Chang A; Nagelberg D; Sharma B; Jeong Y; Diehn M; Wu JC; Morrison AJ; Red-Horse K
[Ad] Endereço:Department of Biology, Stanford University, 371 Serra Mall, Stanford, CA, 94305, USA.
[Ti] Título:Endothelial deletion of Ino80 disrupts coronary angiogenesis and causes congenital heart disease.
[So] Source:Nat Commun;9(1):368, 2018 01 25.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:During development, the formation of a mature, well-functioning heart requires transformation of the ventricular wall from a loose trabecular network into a dense compact myocardium at mid-gestation. Failure to compact is associated in humans with congenital diseases such as left ventricular non-compaction (LVNC). The mechanisms regulating myocardial compaction are however still poorly understood. Here, we show that deletion of the Ino80 chromatin remodeler in vascular endothelial cells prevents ventricular compaction in the developing mouse heart. This correlates with defective coronary vascularization, and specific deletion of Ino80 in the two major coronary progenitor tissues-sinus venosus and endocardium-causes intermediate phenotypes. In vitro, endothelial cells promote myocardial expansion independently of blood flow in an Ino80-dependent manner. Ino80 deletion increases the expression of E2F-activated genes and endothelial cell S-phase occupancy. Thus, Ino80 is essential for coronary angiogenesis and allows coronary vessels to support proper compaction of the heart wall.
[Mh] Termos MeSH primário: Adenosina Trifosfatases/metabolismo
Endotélio Vascular/metabolismo
Cardiopatias Congênitas/metabolismo
Neovascularização Patológica/metabolismo
[Mh] Termos MeSH secundário: Adenosina Trifosfatases/genética
Animais
Vasos Coronários/metabolismo
DNA Helicases/genética
DNA Helicases/metabolismo
Endocárdio/metabolismo
Endocárdio/patologia
Células Endoteliais/enzimologia
Células Endoteliais/metabolismo
Endotélio Vascular/patologia
Cardiopatias Congênitas/genética
Ventrículos do Coração/metabolismo
Ventrículos do Coração/patologia
Seres Humanos
Camundongos Knockout
Camundongos Transgênicos
Miocárdio/metabolismo
Miocárdio/patologia
Neovascularização Patológica/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
EC 3.6.1.- (Adenosine Triphosphatases); EC 3.6.1.- (INO80 protein, mouse); EC 3.6.4.- (DNA Helicases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02796-3


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[PMID]:29302033
[Au] Autor:Ignatenko O; Chilov D; Paetau I; de Miguel E; Jackson CB; Capin G; Paetau A; Terzioglu M; Euro L; Suomalainen A
[Ad] Endereço:Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, Haartmaninkatu 8, University of Helsinki, Helsinki, 00014, Finland.
[Ti] Título:Loss of mtDNA activates astrocytes and leads to spongiotic encephalopathy.
[So] Source:Nat Commun;9(1):70, 2018 01 04.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Mitochondrial dysfunction manifests as different neurological diseases, but the mechanisms underlying the clinical variability remain poorly understood. To clarify whether different brain cells have differential sensitivity to mitochondrial dysfunction, we induced mitochondrial DNA (mtDNA) depletion in either neurons or astrocytes of mice, by inactivating Twinkle (TwKO), the replicative mtDNA helicase. Here we show that astrocytes, the most abundant cerebral cell type, are chronically activated upon mtDNA loss, leading to early-onset spongiotic degeneration of brain parenchyma, microgliosis and secondary neurodegeneration. Neuronal mtDNA loss does not, however, cause symptoms until 8 months of age. Findings in astrocyte-TwKO mimic neuropathology of Alpers syndrome, infantile-onset mitochondrial spongiotic encephalopathy caused by mtDNA maintenance defects. Our evidence indicates that (1) astrocytes are dependent on mtDNA integrity; (2) mitochondrial metabolism contributes to their activation; (3) chronic astrocyte activation has devastating consequences, underlying spongiotic encephalopathy; and that (4) astrocytes are a potential target for interventions.
[Mh] Termos MeSH primário: Astrócitos/metabolismo
Encefalopatias/genética
DNA Mitocondrial/genética
Doenças Mitocondriais/genética
[Mh] Termos MeSH secundário: Animais
Encéfalo/metabolismo
Encéfalo/ultraestrutura
DNA Helicases/genética
DNA Helicases/metabolismo
DNA Mitocondrial/metabolismo
Camundongos Knockout
Microscopia Eletrônica
Proteínas Mitocondriais/genética
Proteínas Mitocondriais/metabolismo
Mutação
Neurônios/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA, Mitochondrial); 0 (Mitochondrial Proteins); EC 3.6.1.- (Peo1 protein, mouse); EC 3.6.4.- (DNA Helicases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-01859-9


  4 / 10382 MEDLINE  
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[PMID]:29298978
[Au] Autor:Lee SI; Celik S; Logsdon BA; Lundberg SM; Martins TJ; Oehler VG; Estey EH; Miller CP; Chien S; Dai J; Saxena A; Blau CA; Becker PS
[Ad] Endereço:Paul G. Allen School of Computer Science and Engineering, University of Washington, 185 E Stevens Way NE, Seattle, WA, 98195, USA. suinlee@cs.washington.edu.
[Ti] Título:A machine learning approach to integrate big data for precision medicine in acute myeloid leukemia.
[So] Source:Nat Commun;9(1):42, 2018 01 03.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cancers that appear pathologically similar often respond differently to the same drug regimens. Methods to better match patients to drugs are in high demand. We demonstrate a promising approach to identify robust molecular markers for targeted treatment of acute myeloid leukemia (AML) by introducing: data from 30 AML patients including genome-wide gene expression profiles and in vitro sensitivity to 160 chemotherapy drugs, a computational method to identify reliable gene expression markers for drug sensitivity by incorporating multi-omic prior information relevant to each gene's potential to drive cancer. We show that our method outperforms several state-of-the-art approaches in identifying molecular markers replicated in validation data and predicting drug sensitivity accurately. Finally, we identify SMARCA4 as a marker and driver of sensitivity to topoisomerase II inhibitors, mitoxantrone, and etoposide, in AML by showing that cell lines transduced to have high SMARCA4 expression reveal dramatically increased sensitivity to these agents.
[Mh] Termos MeSH primário: DNA Helicases/genética
Resistência a Medicamentos Antineoplásicos/genética
Leucemia Mieloide Aguda/genética
Aprendizado de Máquina
Proteínas Nucleares/genética
Medicina de Precisão/métodos
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Algoritmos
Antineoplásicos/farmacologia
Antineoplásicos/uso terapêutico
Biomarcadores Tumorais/metabolismo
Linhagem Celular
Conjuntos de Dados como Assunto
Etoposídeo/farmacologia
Etoposídeo/uso terapêutico
Seres Humanos
Leucemia Mieloide Aguda/tratamento farmacológico
Inibidores da Topoisomerase II/farmacologia
Inibidores da Topoisomerase II/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); 0 (Nuclear Proteins); 0 (Topoisomerase II Inhibitors); 0 (Transcription Factors); 6PLQ3CP4P3 (Etoposide); EC 3.6.1.- (SMARCA4 protein, human); EC 3.6.4.- (DNA Helicases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180105
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02465-5


  5 / 10382 MEDLINE  
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[PMID]:27779108
[Au] Autor:D'Alesio C; Punzi S; Cicalese A; Fornasari L; Furia L; Riva L; Carugo A; Curigliano G; Criscitiello C; Pruneri G; Pelicci PG; Faretta M; Bossi D; Lanfrancone L
[Ad] Endereço:Department of Experimental Oncology, European Institute of Oncology, Milan 20141, Italy.
[Ti] Título:RNAi screens identify CHD4 as an essential gene in breast cancer growth.
[So] Source:Oncotarget;7(49):80901-80915, 2016 Dec 06.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Epigenetic regulation plays an essential role in tumor development and epigenetic modifiers are considered optimal potential druggable candidates. In order to identify new breast cancer vulnerabilities and improve therapeutic chances for patients, we performed in vivo and in vitro shRNA screens in a human breast cancer cell model (MCF10DCIS.com cell line) using epigenetic libraries. Among the genes identified in our screening, we deeply investigated the role of Chromodomain Helicase DNA binding Protein 4 (CHD4) in breast cancer tumorigenesis. CHD4 silencing significantly reduced tumor growth in vivo and proliferation in vitro of MCF10DCIS.com cells. Similarly, in vivo breast cancer growth was decreased in a spontaneous mouse model of breast carcinoma (MMTV-NeuT system) and in metastatic patient-derived xenograft models. Conversely, no reduction in proliferative ability of non-transformed mammary epithelial cells (MCF10A) was detected. Moreover, we showed that CHD4 depletion arrests proliferation by inducing a G0/G1 block of cell cycle associated with up-regulation of CDKN1A (p21). These results highlight the relevance of genetic screens in the identification of tumor frailties and the role of CHD4 as a potential pharmacological target to inhibit breast cancer growth.
[Mh] Termos MeSH primário: Neoplasias da Mama/genética
Proliferação Celular
DNA Helicases/genética
Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/genética
Interferência de RNA
[Mh] Termos MeSH secundário: Animais
Neoplasias da Mama/enzimologia
Neoplasias da Mama/patologia
Pontos de Checagem do Ciclo Celular
Linhagem Celular Tumoral
Biologia Computacional
Inibidor de Quinase Dependente de Ciclina p21/genética
Inibidor de Quinase Dependente de Ciclina p21/metabolismo
DNA Helicases/metabolismo
Feminino
Regulação Neoplásica da Expressão Gênica
Biblioteca Gênica
Redes Reguladoras de Genes
Predisposição Genética para Doença
Seres Humanos
Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/metabolismo
Camundongos Endogâmicos NOD
Camundongos SCID
Transplante de Neoplasias
Fenótipo
Transdução de Sinais
Fatores de Tempo
Carga Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CDKN1A protein, human); 0 (CHD4 protein, human); 0 (Cdkn1a protein, mouse); 0 (Cyclin-Dependent Kinase Inhibitor p21); EC 3.5.1.98 (Mi-2 Nucleosome Remodeling and Deacetylase Complex); EC 3.6.1.3 (Mi-2beta protein, mouse); EC 3.6.4.- (DNA Helicases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.12646


  6 / 10382 MEDLINE  
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[PMID]:29233693
[Au] Autor:Hidese R; Kawato K; Nakura Y; Fujiwara A; Yasukawa K; Yanagihara I; Fujiwara S
[Ad] Endereço:Department of Bioscience, Graduate School of Science and Technology, Kwansei-Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan.
[Ti] Título:Thermostable DNA helicase improves the sensitivity of digital PCR.
[So] Source:Biochem Biophys Res Commun;495(3):2189-2194, 2018 01 15.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:DNA/RNA helicases, which catalyze the unwinding of duplex nucleic acids using the energy of ATP hydrolysis, contribute to various biological functions involving DNA or RNA. Euryarchaeota-specific helicase Tk-EshA (superfamily 2) from the hyperthermophilic archaeon Thermococcus kodakarensis has been used to decrease generation of mis-amplified products (noise DNAs) during PCR. In this study, we focused on another type (superfamily 1B) of helicase, Tk-Upf1 (TK0178) from T. kodakarensis, and compared its effectiveness in PCR and digital PCR with that of Tk-EshA. For this purpose, we obtained Tk-Upf1 as a recombinant protein and assessed its enzymatic characteristics. Among various double-stranded DNA (dsDNA) substrates (forked, 5' overhung, 3' overhung, and blunt-ended duplex), Tk-Upf1 had the highest unwinding activity toward 5' overhung DNAs. Noise DNAs were also eliminated in the presence of Tk-Upf1 at concentrations 10-fold lower than those required to yield a comparable reduction with Tk-EshA. When a 5' or 3' overhung mis-annealed primer was included as a competitive primer along with specific primers, noise DNAs derived from the mis-annealed primer were eliminated in the presence of Tk-Upf1. In digital PCR, addition of Tk-EshA or Tk-Upf1 increased fluorescent intensities and improved separation between common and risk allele clusters, indicating that both helicases functioned as signal enhancers. In comparison with Tk-EshA, a smaller amount of Tk-Upf1 was required to improve the performance of digital PCR.
[Mh] Termos MeSH primário: Artefatos
DNA Helicases/química
DNA Helicases/genética
DNA/química
DNA/genética
Reação em Cadeia da Polimerase/métodos
[Mh] Termos MeSH secundário: Algoritmos
Interpretação Estatística de Dados
Ativação Enzimática
Estabilidade Enzimática
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Especificidade por Substrato
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
9007-49-2 (DNA); EC 3.6.4.- (DNA Helicases)
[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:171214
[St] Status:MEDLINE


  7 / 10382 MEDLINE  
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[PMID]:28457855
[Au] Autor:Tan CW; Sam IC; Chong WL; Lee VS; Chan YF
[Ad] Endereço:Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: tancw86@gmail.com.
[Ti] Título:Polysulfonate suramin inhibits Zika virus infection.
[So] Source:Antiviral Res;143:186-194, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log PFU viral reduction with IC value of ∼2.5-5 µg/ml (1.93 µM-3.85 µM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor.
[Mh] Termos MeSH primário: Suramina/antagonistas & inibidores
Infecção pelo Zika virus/prevenção & controle
Zika virus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais
Cercopithecus aethiops
Cloratos/farmacologia
DNA Helicases/metabolismo
Sulfato de Dextrana/antagonistas & inibidores
Flavivirus/efeitos dos fármacos
Glicosaminoglicanos/farmacologia
Heparina/análogos & derivados
Heparina/química
Heparina/farmacologia
Heparitina Sulfato/farmacologia
Concentração Inibidora 50
Camundongos
Simulação de Acoplamento Molecular
Simulação de Dinâmica Molecular
RNA Helicases/química
RNA Helicases/efeitos dos fármacos
Serina Endopeptidases/química
Serina Endopeptidases/efeitos dos fármacos
Suramina/administração & dosagem
Células Vero
Proteínas do Envelope Viral/metabolismo
Proteínas não Estruturais Virais/química
Proteínas não Estruturais Virais/efeitos dos fármacos
Internalização do Vírus/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
Zika virus/fisiologia
Infecção pelo Zika virus/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Chlorates); 0 (Glycosaminoglycans); 0 (NS3 protein, flavivirus); 0 (Viral Envelope Proteins); 0 (Viral Nonstructural Proteins); 6032D45BEM (Suramin); 9005-49-6 (Heparin); 9042-14-2 (Dextran Sulfate); 9050-30-0 (Heparitin Sulfate); EC 3.4.21.- (Serine Endopeptidases); EC 3.6.4.- (DNA Helicases); EC 3.6.4.13 (RNA Helicases); T95DR77GMR (sodium chlorate)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


  8 / 10382 MEDLINE  
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[PMID]:29341672
[Au] Autor:Lin W; Ma J; Nong D; Xu C; Zhang B; Li J; Jia Q; Dou S; Ye F; Xi X; Lu Y; Li M
[Ad] Endereço:Beijing National Laboratory for Condensed Matter Physics and CAS Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
[Ti] Título:Helicase Stepping Investigated with One-Nucleotide Resolution Fluorescence Resonance Energy Transfer.
[So] Source:Phys Rev Lett;119(13):138102, 2017 Sep 29.
[Is] ISSN:1079-7114
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Single-molecule Förster resonance energy transfer is widely applied to study helicases by detecting distance changes between a pair of dyes anchored to overhangs of a forked DNA. However, it has been lacking single-base pair (1-bp) resolution required for revealing stepping kinetics of helicases. We designed a nanotensioner in which a short DNA is bent to exert force on the overhangs, just as in optical or magnetic tweezers. The strategy improved the resolution of Förster resonance energy transfer to 0.5 bp, high enough to uncover differences in DNA unwinding by yeast Pif1 and E. coli RecQ whose unwinding behaviors cannot be differentiated by currently practiced methods. We found that Pif1 exhibits 1-bp-stepping kinetics, while RecQ breaks 1 bp at a time but sequesters the nascent nucleotides and releases them randomly. The high-resolution data allowed us to propose a three-parameter model to quantitatively interpret the apparently different unwinding behaviors of the two helicases which belong to two superfamilies.
[Mh] Termos MeSH primário: DNA Helicases/metabolismo
DNA/química
Escherichia coli/metabolismo
[Mh] Termos MeSH secundário: Transferência Ressonante de Energia de Fluorescência
Cinética
Conformação de Ácido Nucleico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9007-49-2 (DNA); EC 3.6.4.- (DNA Helicases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1103/PhysRevLett.119.138102


  9 / 10382 MEDLINE  
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[PMID]:29220652
[Au] Autor:Lehmann LC; Hewitt G; Aibara S; Leitner A; Marklund E; Maslen SL; Maturi V; Chen Y; van der Spoel D; Skehel JM; Moustakas A; Boulton SJ; Deindl S
[Ad] Endereço:Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, 75124 Uppsala, Sweden.
[Ti] Título:Mechanistic Insights into Autoinhibition of the Oncogenic Chromatin Remodeler ALC1.
[So] Source:Mol Cell;68(5):847-859.e7, 2017 Dec 07.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human ALC1 is an oncogene-encoded chromatin-remodeling enzyme required for DNA repair that possesses a poly(ADP-ribose) (PAR)-binding macro domain. Its engagement with PARylated PARP1 activates ALC1 at sites of DNA damage, but the underlying mechanism remains unclear. Here, we establish a dual role for the macro domain in autoinhibition of ALC1 ATPase activity and coupling to nucleosome mobilization. In the absence of DNA damage, an inactive conformation of the ATPase is maintained by juxtaposition of the macro domain against predominantly the C-terminal ATPase lobe through conserved electrostatic interactions. Mutations within this interface displace the macro domain, constitutively activate the ALC1 ATPase independent of PARylated PARP1, and alter the dynamics of ALC1 recruitment at DNA damage sites. Upon DNA damage, binding of PARylated PARP1 by the macro domain induces a conformational change that relieves autoinhibitory interactions with the ATPase motor, which selectively activates ALC1 remodeling upon recruitment to sites of DNA damage.
[Mh] Termos MeSH primário: Montagem e Desmontagem da Cromatina
Dano ao DNA
DNA Helicases/metabolismo
Reparo do DNA
Proteínas de Ligação a DNA/metabolismo
Nucleossomos/enzimologia
[Mh] Termos MeSH secundário: Domínio Catalítico
Linhagem Celular Tumoral
DNA Helicases/química
DNA Helicases/genética
Proteínas de Ligação a DNA/química
Proteínas de Ligação a DNA/genética
Ativação Enzimática
Seres Humanos
Microscopia Eletrônica
Simulação de Dinâmica Molecular
Mutação
Nucleossomos/química
Poli(ADP-Ribose) Polimerase-1/química
Poli(ADP-Ribose) Polimerase-1/metabolismo
Poli ADP Ribosilação
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Transporte Proteico
Espalhamento a Baixo Ângulo
Eletricidade Estática
Relação Estrutura-Atividade
Fatores de Tempo
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (Nucleosomes); EC 2.4.2.30 (PARP1 protein, human); EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1); EC 3.6.4.- (DNA Helicases); EC 3.6.4.12 (CHD1L protein, human)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


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[PMID]:28743747
[Au] Autor:Bermek O; Weller SK; Griffith JD
[Ad] Endereço:From the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295 and oya_bermek@med.unc.edu.
[Ti] Título:The UL8 subunit of the helicase-primase complex of herpes simplex virus promotes DNA annealing and has a high affinity for replication forks.
[So] Source:J Biol Chem;292(38):15611-15621, 2017 09 22.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During lytic infection, herpes simplex virus (HSV) DNA is replicated by a mechanism involving DNA recombination. For instance, replication of the HSV-1 genome produces X- and Y-branched structures, reminiscent of recombination intermediates. HSV-1's replication machinery includes a trimeric helicase-primase composed of helicase (UL5) and primase (UL52) subunits and a third subunit, UL8. UL8 has been reported to stimulate the helicase and primase activities of the complex in the presence of ICP8, an HSV-1 protein that functions as an annealase, a protein that binds complementary single-stranded DNA (ssDNA) and facilitates its annealing to duplex DNA. UL8 also influences the intracellular localization of the UL5/UL52 subunits, but UL8's catalytic activities are not known. In this study we used a combination of biochemical techniques and transmission electron microscopy. First, we report that UL8 alone forms protein filaments in solution. Moreover, we also found that UL8 binds to ssDNAs >50-nucletides long and promotes the annealing of complementary ssDNA to generate highly branched duplex DNA structures. Finally, UL8 has a very high affinity for replication fork structures containing a gap in the lagging strand as short as 15 nucleotides, suggesting that UL8 may aid in directing or loading the trimeric complex onto a replication fork. The properties of UL8 uncovered here suggest that UL8 may be involved in the generation of the X- and Y-branched structures that are the hallmarks of HSV replication.
[Mh] Termos MeSH primário: DNA Helicases/metabolismo
DNA Primase/metabolismo
Replicação do DNA
Herpesvirus Humano 1/enzimologia
Herpesvirus Humano 1/genética
Proteínas Virais/metabolismo
[Mh] Termos MeSH secundário: Sequência de Bases
DNA de Cadeia Simples/biossíntese
DNA de Cadeia Simples/química
DNA de Cadeia Simples/metabolismo
Herpesvirus Humano 1/ultraestrutura
Peso Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (DNA, Single-Stranded); 0 (Viral Proteins); EC 2.7.7.- (DNA Primase); EC 3.1.- (helicase-primase, Human herpesvirus 1); EC 3.6.4.- (DNA Helicases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171230
[Lr] Data última revisão:
171230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.799064



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