Base de dados : MEDLINE
Pesquisa : D12.776.260.700 [Categoria DeCS]
Referências encontradas : 1273 [refinar]
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[PMID]:29320546
[Au] Autor:Krasikova YS; Rechkunova NI; Maltseva EA; Lavrik OI
[Ad] Endereço:Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia.
[Ti] Título:RPA and XPA interaction with DNA structures mimicking intermediates of the late stages in nucleotide excision repair.
[So] Source:PLoS One;13(1):e0190782, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Replication protein A (RPA) and the xeroderma pigmentosum group A (XPA) protein are indispensable for both pathways of nucleotide excision repair (NER). Here we analyze the interaction of RPA and XPA with DNA containing a flap and different size gaps that imitate intermediates of the late NER stages. Using gel mobility shift assays, we found that RPA affinity for DNA decreased when DNA contained both extended gap and similar sized flap in comparison with gapped-DNA structure. Moreover, crosslinking experiments with the flap-gap DNA revealed that RPA interacts mainly with the ssDNA platform within the long gap and contacts flap in DNA with a short gap. XPA exhibits higher affinity for bubble-DNA structures than to flap-gap-containing DNA. Protein titration analysis showed that formation of the RPA-XPA-DNA ternary complex depends on the protein concentration ratio and these proteins can function as independent players or in tandem. Using fluorescently-labelled RPA, direct interaction of this protein with XPA was detected and characterized quantitatively. The data obtained allow us to suggest that XPA can be involved in the post-incision NER stages via its interaction with RPA.
[Mh] Termos MeSH primário: Reparo do DNA
DNA/metabolismo
Proteína de Replicação A/metabolismo
Proteína de Xeroderma Pigmentoso Grupo A/metabolismo
[Mh] Termos MeSH secundário: DNA/química
Ensaio de Desvio de Mobilidade Eletroforética
Seres Humanos
Marcadores de Fotoafinidade
Ligação Proteica
Proteínas Recombinantes/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Photoaffinity Labels); 0 (Recombinant Proteins); 0 (Replication Protein A); 0 (Xeroderma Pigmentosum Group A Protein); 9007-49-2 (DNA)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190782


  2 / 1273 MEDLINE  
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[PMID]:28467896
[Au] Autor:Postigo A; Ramsden AE; Howell M; Way M
[Ad] Endereço:Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT London, UK.
[Ti] Título:Cytoplasmic ATR Activation Promotes Vaccinia Virus Genome Replication.
[So] Source:Cell Rep;19(5):1022-1032, 2017 May 02.
[Is] ISSN:2211-1247
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In contrast to most DNA viruses, poxviruses replicate their genomes in the cytoplasm without host involvement. We find that vaccinia virus induces cytoplasmic activation of ATR early during infection, before genome uncoating, which is unexpected because ATR plays a fundamental nuclear role in maintaining host genome integrity. ATR, RPA, INTS7, and Chk1 are recruited to cytoplasmic DNA viral factories, suggesting canonical ATR pathway activation. Consistent with this, pharmacological and RNAi-mediated inhibition of canonical ATR signaling suppresses genome replication. RPA and the sliding clamp PCNA interact with the viral polymerase E9 and are required for DNA replication. Moreover, the ATR activator TOPBP1 promotes genome replication and associates with the viral replisome component H5. Our study suggests that, in contrast to long-held beliefs, vaccinia recruits conserved components of the eukaryote DNA replication and repair machinery to amplify its genome in the host cytoplasm.
[Mh] Termos MeSH primário: Genoma Viral
Interações Hospedeiro-Patógeno
Vírus Vaccinia/fisiologia
Replicação Viral
[Mh] Termos MeSH secundário: Animais
Proteínas Mutadas de Ataxia Telangiectasia/genética
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
Proteínas de Transporte/metabolismo
Linhagem Celular
Cercopithecus aethiops
Quinase do Ponto de Checagem 1/metabolismo
Proteínas de Ligação a DNA/metabolismo
Células HeLa
Seres Humanos
Proteínas Nucleares/metabolismo
Antígeno Nuclear de Célula em Proliferação/metabolismo
Proteína de Replicação A/metabolismo
Vírus Vaccinia/genética
Vírus Vaccinia/patogenicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (DNA-Binding Proteins); 0 (Nuclear Proteins); 0 (Proliferating Cell Nuclear Antigen); 0 (Replication Protein A); 0 (TOPBP1 protein, human); EC 2.7.11.1 (ATR protein, human); EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins); EC 2.7.11.1 (CHEK1 protein, human); EC 2.7.11.1 (Checkpoint Kinase 1)
[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


  3 / 1273 MEDLINE  
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[PMID]:29033322
[Au] Autor:Deshpande I; Seeber A; Shimada K; Keusch JJ; Gut H; Gasser SM
[Ad] Endereço:Friedrich Miescher Institute for Biomedical Research (FMI), Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Faculty of Natural Sciences, Klingelbergstrasse 50, 4056 Basel, Switzerland.
[Ti] Título:Structural Basis of Mec1-Ddc2-RPA Assembly and Activation on Single-Stranded DNA at Sites of Damage.
[So] Source:Mol Cell;68(2):431-445.e5, 2017 Oct 19.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mec1-Ddc2 (ATR-ATRIP) is a key DNA-damage-sensing kinase that is recruited through the single-stranded (ss) DNA-binding replication protein A (RPA) to initiate the DNA damage checkpoint response. Activation of ATR-ATRIP in the absence of DNA damage is lethal. Therefore, it is important that damage-specific recruitment precedes kinase activation, which is achieved at least in part by Mec1-Ddc2 homodimerization. Here, we report a structural, biochemical, and functional characterization of the yeast Mec1-Ddc2-RPA assembly. High-resolution co-crystal structures of Ddc2-Rfa1 and Ddc2-Rfa1-t11 (K45E mutant) N termini and of the Ddc2 coiled-coil domain (CCD) provide insight into Mec1-Ddc2 homodimerization and damage-site targeting. Based on our structural and functional findings, we present a Mec1-Ddc2-RPA-ssDNA composite structural model. By way of validation, we show that RPA-dependent recruitment of Mec1-Ddc2 is crucial for maintaining its homodimeric state at ssDNA and that Ddc2's recruitment domain and CCD are important for Mec1-dependent survival of UV-light-induced DNA damage.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/química
Proteínas de Ciclo Celular/química
DNA Fúngico/química
DNA de Cadeia Simples/química
Peptídeos e Proteínas de Sinalização Intracelular/química
Modelos Moleculares
Proteínas Serina-Treonina Quinases/química
Proteína de Replicação A/química
Proteínas de Saccharomyces cerevisiae/química
Saccharomyces cerevisiae/química
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/genética
Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Substituição de Aminoácidos
Proteínas de Ciclo Celular/genética
Proteínas de Ciclo Celular/metabolismo
Cristalografia por Raios X
DNA Fúngico/genética
DNA Fúngico/metabolismo
DNA de Cadeia Simples/genética
DNA de Cadeia Simples/metabolismo
Peptídeos e Proteínas de Sinalização Intracelular/genética
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Mutação de Sentido Incorreto
Estrutura Quaternária de Proteína
Estrutura Secundária de Proteína
Proteínas Serina-Treonina Quinases/genética
Proteínas Serina-Treonina Quinases/metabolismo
Proteína de Replicação A/genética
Proteína de Replicação A/metabolismo
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/metabolismo
Proteínas de Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Cell Cycle Proteins); 0 (DNA, Fungal); 0 (DNA, Single-Stranded); 0 (Intracellular Signaling Peptides and Proteins); 0 (LCD1 protein, S cerevisiae); 0 (RFA1 protein, S cerevisiae); 0 (Replication Protein A); 0 (Saccharomyces cerevisiae Proteins); EC 2.7.11.1 (MEC1 protein, S cerevisiae); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171017
[St] Status:MEDLINE


  4 / 1273 MEDLINE  
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[PMID]:28934470
[Au] Autor:Pokhrel N; Origanti S; Davenport EP; Gandhi D; Kaniecki K; Mehl RA; Greene EC; Dockendorff C; Antony E
[Ad] Endereço:Department of Biological Sciences, Marquette University, Milwaukee, WI 53201, USA.
[Ti] Título:Monitoring Replication Protein A (RPA) dynamics in homologous recombination through site-specific incorporation of non-canonical amino acids.
[So] Source:Nucleic Acids Res;45(16):9413-9426, 2017 Sep 19.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:An essential coordinator of all DNA metabolic processes is Replication Protein A (RPA). RPA orchestrates these processes by binding to single-stranded DNA (ssDNA) and interacting with several other DNA binding proteins. Determining the real-time kinetics of single players such as RPA in the presence of multiple DNA processors to better understand the associated mechanistic events is technically challenging. To overcome this hurdle, we utilized non-canonical amino acids and bio-orthogonal chemistry to site-specifically incorporate a chemical fluorophore onto a single subunit of heterotrimeric RPA. Upon binding to ssDNA, this fluorescent RPA (RPAf) generates a quantifiable change in fluorescence, thus serving as a reporter of its dynamics on DNA in the presence of multiple other DNA binding proteins. Using RPAf, we describe the kinetics of facilitated self-exchange and exchange by Rad51 and mediator proteins during various stages in homologous recombination. RPAf is widely applicable to investigate its mechanism of action in processes such as DNA replication, repair and telomere maintenance.
[Mh] Termos MeSH primário: Recombinação Homóloga
Proteína de Replicação A/química
Proteína de Replicação A/metabolismo
Proteínas de Saccharomyces cerevisiae/química
Proteínas de Saccharomyces cerevisiae/metabolismo
[Mh] Termos MeSH secundário: Azidas/química
DNA de Cadeia Simples/metabolismo
Corantes Fluorescentes/química
Microscopia de Fluorescência
Fenilalanina/análogos & derivados
Fenilalanina/química
Rad51 Recombinase/metabolismo
Proteína de Replicação A/genética
Proteínas de Saccharomyces cerevisiae/genética
Triptofano/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Azides); 0 (DNA, Single-Stranded); 0 (Fluorescent Dyes); 0 (RFA1 protein, S cerevisiae); 0 (Replication Protein A); 0 (Saccharomyces cerevisiae Proteins); 33173-53-4 (4-azidophenylalanine); 47E5O17Y3R (Phenylalanine); 8DUH1N11BX (Tryptophan); EC 2.7.7.- (RAD51 protein, S cerevisiae); EC 2.7.7.- (Rad51 Recombinase)
[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:170922
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx598


  5 / 1273 MEDLINE  
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[PMID]:28837865
[Au] Autor:Tian Y; Liu G; Wang H; Tian Z; Cai Z; Zhang F; Luo Y; Wang S; Guo G; Wang X; Powell S; Feng Z
[Ad] Endereço:Department of Occupational Health and Occupational Medicine, The Public Health School, Shandong University, Shandong, Jinan, 250012, China.
[Ti] Título:Valproic acid sensitizes breast cancer cells to hydroxyurea through inhibiting RPA2 hyperphosphorylation-mediated DNA repair pathway.
[So] Source:DNA Repair (Amst);58:1-12, 2017 Oct.
[Is] ISSN:1568-7856
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:It was reported that valproic acid (VPA, a histone deacetylase inhibitor) can sensitize cancer cells to hydroxyurea (HU, a ribonucleotide reductase inhibitor) for chemotherapy, although the mechanism of VPA-induced HU sensitization is unclear. In this study, we systematically characterized VPA-induced HU sensitization of breast cancer cells. Multiple breast cancer cell models were employed to investigate whether the safe concentration of 0.5mM VPA and 2mM HU can result in DNA double-strand breaks (DSBs) and impact cell survival. Furthermore, the underlying mechanism was explored through cell biology assays, including clonogenic survival, homologous recombination (HR) activity, immunoblot and immunofluorescence. We found that VPA and HU cooperatively suppressed cancer cell survival. VPA resulted in the accumulation of more DNA double-strand breaks (DSBs) in response to HU-induced replication arrest and was able to block HU-stimulated homologous recombination (HR) through inhibiting the activity of two key HR repair proteins by hyperphosphorylation of replication protein A2 (RPA2-p) and recombinase Rad51. However, apoptosis was not detected under this condition. In addition, the results from the survival fraction in the cells expressing defective RPA2-p showed that VPA disrupted the HU-induced RPA2-p-Rad51-mediated HR pathway. Importantly, these findings were further supported by analyzing primary-culture cells from the tissue of chemical carcinogen (DMBA)-induced breast cancer in rats. Thus, our data demonstrated that VPA and HU synergistically suppressed tumor cells via disturbing RPA2-p-mediated DNA repair pathway, which provides a new way for combining chemotherapeutic drugs to sensitize breast cancer cells.
[Mh] Termos MeSH primário: Neoplasias da Mama/tratamento farmacológico
Hidroxiureia/uso terapêutico
Reparo de DNA por Recombinação/efeitos dos fármacos
Proteína de Replicação A/antagonistas & inibidores
Ácido Valproico/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias da Mama/metabolismo
DNA/metabolismo
Quebras de DNA de Cadeia Dupla
Replicação do DNA/efeitos dos fármacos
Feminino
Seres Humanos
Rad51 Recombinase/metabolismo
Ratos
Proteína de Replicação A/metabolismo
Ácido Valproico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Replication Protein A); 0 (Rpa2 protein, rat); 614OI1Z5WI (Valproic Acid); 9007-49-2 (DNA); EC 2.7.7.- (Rad51 Recombinase); X6Q56QN5QC (Hydroxyurea)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170825
[St] Status:MEDLINE


  6 / 1273 MEDLINE  
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[PMID]:28806726
[Au] Autor:Iyer DR; Rhind N
[Ad] Endereço:Department of Biochemistry & Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
[Ti] Título:Replication fork slowing and stalling are distinct, checkpoint-independent consequences of replicating damaged DNA.
[So] Source:PLoS Genet;13(8):e1006958, 2017 Aug.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In response to DNA damage during S phase, cells slow DNA replication. This slowing is orchestrated by the intra-S checkpoint and involves inhibition of origin firing and reduction of replication fork speed. Slowing of replication allows for tolerance of DNA damage and suppresses genomic instability. Although the mechanisms of origin inhibition by the intra-S checkpoint are understood, major questions remain about how the checkpoint regulates replication forks: Does the checkpoint regulate the rate of fork progression? Does the checkpoint affect all forks, or only those encountering damage? Does the checkpoint facilitate the replication of polymerase-blocking lesions? To address these questions, we have analyzed the checkpoint in the fission yeast Schizosaccharomyces pombe using a single-molecule DNA combing assay, which allows us to unambiguously separate the contribution of origin and fork regulation towards replication slowing, and allows us to investigate the behavior of individual forks. Moreover, we have interrogated the role of forks interacting with individual sites of damage by using three damaging agents-MMS, 4NQO and bleomycin-that cause similar levels of replication slowing with very different frequency of DNA lesions. We find that the checkpoint slows replication by inhibiting origin firing, but not by decreasing fork rates. However, the checkpoint appears to facilitate replication of damaged templates, allowing forks to more quickly pass lesions. Finally, using a novel analytic approach, we rigorously identify fork stalling events in our combing data and show that they play a previously unappreciated role in shaping replication kinetics in response to DNA damage.
[Mh] Termos MeSH primário: Dano ao DNA
Replicação do DNA
Regulação Fúngica da Expressão Gênica
Pontos de Checagem da Fase S do Ciclo Celular
Schizosaccharomyces/genética
[Mh] Termos MeSH secundário: 4-Nitroquinolina-1-Óxido
Bleomicina
DNA Fúngico/genética
Metanossulfonato de Metila
Proteína de Replicação A/genética
Proteína de Replicação A/metabolismo
Proteínas de Schizosaccharomyces pombe/genética
Proteínas de Schizosaccharomyces pombe/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Fungal); 0 (Replication Protein A); 0 (Schizosaccharomyces pombe Proteins); 11056-06-7 (Bleomycin); 56-57-5 (4-Nitroquinoline-1-oxide); AT5C31J09G (Methyl Methanesulfonate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170913
[Lr] Data última revisão:
170913
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170815
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006958


  7 / 1273 MEDLINE  
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[PMID]:28666352
[Au] Autor:Dubois JC; Yates M; Gaudreau-Lapierre A; Clément G; Cappadocia L; Gaudreau L; Zou L; Maréchal A
[Ad] Endereço:Department of Biology, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
[Ti] Título:A phosphorylation-and-ubiquitylation circuitry driving ATR activation and homologous recombination.
[So] Source:Nucleic Acids Res;45(15):8859-8872, 2017 Sep 06.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:RPA-coated single-stranded DNA (RPA-ssDNA), a nucleoprotein structure induced by DNA damage, promotes ATR activation and homologous recombination (HR). RPA is hyper-phosphorylated and ubiquitylated after DNA damage. The ubiquitylation of RPA by PRP19 and RFWD3 facilitates ATR activation and HR, but how it is stimulated by DNA damage is still unclear. Here, we show that RFWD3 binds RPA constitutively, whereas PRP19 recognizes RPA after DNA damage. The recruitment of PRP19 by RPA depends on PIKK-mediated RPA phosphorylation and a positively charged pocket in PRP19. An RPA32 mutant lacking phosphorylation sites fails to recruit PRP19 and support RPA ubiquitylation. PRP19 mutants unable to bind RPA or lacking ubiquitin ligase activity also fail to support RPA ubiquitylation and HR. These results suggest that RPA phosphorylation enhances the recruitment of PRP19 to RPA-ssDNA and stimulates RPA ubiquitylation through a process requiring both PRP19 and RFWD3, thereby triggering a phosphorylation-ubiquitylation circuitry that promotes ATR activation and HR.
[Mh] Termos MeSH primário: Enzimas Reparadoras do DNA/genética
Reparo do DNA
DNA de Cadeia Simples/genética
Recombinação Homóloga
Proteínas Nucleares/genética
Fatores de Processamento de RNA/genética
Proteína de Replicação A/genética
[Mh] Termos MeSH secundário: Proteínas Mutadas de Ataxia Telangiectasia/genética
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
Linhagem Celular Tumoral
Dano ao DNA
Enzimas Reparadoras do DNA/química
Enzimas Reparadoras do DNA/metabolismo
Replicação do DNA
DNA de Cadeia Simples/metabolismo
Regulação da Expressão Gênica
Células HEK293
Células HeLa
Seres Humanos
Proteínas Nucleares/química
Proteínas Nucleares/metabolismo
Osteoblastos/citologia
Osteoblastos/metabolismo
Fosforilação
Fatores de Processamento de RNA/química
Fatores de Processamento de RNA/metabolismo
Proteína de Replicação A/metabolismo
Transdução de Sinais
Ubiquitina-Proteína Ligases/genética
Ubiquitina-Proteína Ligases/metabolismo
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Single-Stranded); 0 (Nuclear Proteins); 0 (RNA Splicing Factors); 0 (Replication Protein A); EC 2.3.2.27 (RFWD3 protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.11.1 (ATR protein, human); EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins); EC 6.5.1.- (DNA Repair Enzymes); EC 6.5.1.- (PRPF19 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170702
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx571


  8 / 1273 MEDLINE  
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[PMID]:28640365
[Au] Autor:Ryu JS; Koo HS
[Ad] Endereço:Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul, Korea.
[Ti] Título:The Caenorhabditis elegans WRN helicase promotes double-strand DNA break repair by mediating end resection and checkpoint activation.
[So] Source:FEBS Lett;591(14):2155-2166, 2017 Jul.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The protein associated with Werner syndrome (WRN), is involved in DNA repair, checkpoint activation, and telomere maintenance. To better understand the involvement of WRN in double-strand DNA break (DSB) repair, we analyzed the combinatorial role of WRN-1, the Caenorhabditis elegans WRN helicase, in conjunction with EXO-1 and DNA-2 nucleases. We found that WRN-1 cooperates with DNA-2 to resect DSB ends in a pathway acting in parallel to EXO-1. The wrn-1 mutants show an aberrant accumulation of replication protein A (RPA) and RAD-51, and the same pattern of accumulation is also observed in checkpoint-defective strains. We conclude that WRN-1 plays a conserved role in the resection of DSB ends and mediates checkpoint signaling, thereby influencing levels of RPA and RAD-51.
[Mh] Termos MeSH primário: Proteínas de Caenorhabditis elegans/metabolismo
Caenorhabditis elegans/enzimologia
Caenorhabditis elegans/genética
Pontos de Checagem do Ciclo Celular
Quebras de DNA de Cadeia Dupla
DNA Helicases/metabolismo
Reparo do DNA
[Mh] Termos MeSH secundário: Animais
Caenorhabditis elegans/citologia
Caenorhabditis elegans/efeitos da radiação
Proteínas de Caenorhabditis elegans/genética
Pontos de Checagem do Ciclo Celular/efeitos da radiação
DNA Helicases/genética
Reparo do DNA/efeitos da radiação
Endodesoxirribonucleases/genética
Endodesoxirribonucleases/metabolismo
Raios gama
Mutação
Rad51 Recombinase/metabolismo
Proteína de Replicação A/metabolismo
[Pt] Tipo de publicação:LETTER
[Nm] Nome de substância:
0 (Caenorhabditis elegans Proteins); 0 (Replication Protein A); EC 2.7.7.- (Rad51 Recombinase); EC 2.7.7.- (rad-51 protein, C elegans); EC 3.1.- (Endodeoxyribonucleases); EC 3.6.4.- (DNA Helicases); EC 3.6.4.12 (dna-2 protein, C elegans); EC 5.99.- (WRN-1 protein, C elegans)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170815
[Lr] Data última revisão:
170815
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12724


  9 / 1273 MEDLINE  
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[PMID]:28622519
[Au] Autor:Toledo L; Neelsen KJ; Lukas J
[Ad] Endereço:Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark; Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark. Electronic address: ltoledo@sund.ku.dk.
[Ti] Título:Replication Catastrophe: When a Checkpoint Fails because of Exhaustion.
[So] Source:Mol Cell;66(6):735-749, 2017 Jun 15.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Proliferating cells rely on the so-called DNA replication checkpoint to ensure orderly completion of genome duplication, and its malfunction may lead to catastrophic genome disruption, including unscheduled firing of replication origins, stalling and collapse of replication forks, massive DNA breakage, and, ultimately, cell death. Despite many years of intensive research into the molecular underpinnings of the eukaryotic replication checkpoint, the mechanisms underlying the dismal consequences of its failure remain enigmatic. A recent development offers a unifying model in which the replication checkpoint guards against global exhaustion of rate-limiting replication regulators. Here we discuss how such a mechanism can prevent catastrophic genome disruption and suggest how to harness this knowledge to advance therapeutic strategies to eliminate cancer cells that inherently proliferate under increased DNA replication stress.
[Mh] Termos MeSH primário: Proliferação Celular
Dano ao DNA
Reparo do DNA
Replicação do DNA
DNA/biossíntese
Instabilidade Genômica
Neoplasias/metabolismo
[Mh] Termos MeSH secundário: Animais
Morte Celular
DNA/genética
Seres Humanos
Neoplasias/genética
Neoplasias/patologia
Neoplasias/terapia
Proteína de Replicação A/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Replication Protein A); 9007-49-2 (DNA)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170617
[St] Status:MEDLINE


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[PMID]:28607004
[Au] Autor:Abdullah UB; McGouran JF; Brolih S; Ptchelkine D; El-Sagheer AH; Brown T; McHugh PJ
[Ad] Endereço:Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
[Ti] Título:RPA activates the XPF-ERCC1 endonuclease to initiate processing of DNA interstrand crosslinks.
[So] Source:EMBO J;36(14):2047-2060, 2017 Jul 14.
[Is] ISSN:1460-2075
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:During replication-coupled DNA interstrand crosslink (ICL) repair, the XPF-ERCC1 endonuclease is required for the incisions that release, or "unhook", ICLs, but the mechanism of ICL unhooking remains largely unknown. Incisions are triggered when the nascent leading strand of a replication fork strikes the ICL Here, we report that while purified XPF-ERCC1 incises simple ICL-containing model replication fork structures, the presence of a nascent leading strand, modelling the effects of replication arrest, inhibits this activity. Strikingly, the addition of the single-stranded DNA (ssDNA)-binding replication protein A (RPA) selectively restores XPF-ERCC1 endonuclease activity on this structure. The 5'-3' exonuclease SNM1A can load from the XPF-ERCC1-RPA-induced incisions and digest past the crosslink to quantitatively complete the unhooking reaction. We postulate that these collaborative activities of XPF-ERCC1, RPA and SNM1A might explain how ICL unhooking is achieved .
[Mh] Termos MeSH primário: Reparo do DNA
Proteínas de Ligação a DNA/metabolismo
Endonucleases/metabolismo
Exodesoxirribonucleases/metabolismo
Proteína de Replicação A/metabolismo
[Mh] Termos MeSH secundário: Seres Humanos
Modelos Biológicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (RPA1 protein, human); 0 (Replication Protein A); 0 (xeroderma pigmentosum group F protein); EC 3.1.- (DCLRE1A protein, human); EC 3.1.- (ERCC1 protein, human); EC 3.1.- (Endonucleases); EC 3.1.- (Exodeoxyribonucleases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170727
[Lr] Data última revisão:
170727
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170614
[St] Status:MEDLINE
[do] DOI:10.15252/embj.201796664



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