Base de dados : MEDLINE
Pesquisa : D13.695.201 [Categoria DeCS]
Referências encontradas : 3141 [refinar]
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[PMID]:29327000
[Au] Autor:Nikolaienko TY; Bulavin LA
[Ad] Endereço:Taras Shevchenko National University of Kyiv, Faculty of Physics, 64/13, Volodymyrska Street, City of Kyiv, 01601, Ukraine. tim_mail@ukr.net.
[Ti] Título:Atomic charges for conformationally rich molecules obtained through a modified principal component regression.
[So] Source:Phys Chem Chem Phys;20(4):2890-2903, 2018 Jan 24.
[Is] ISSN:1463-9084
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A modification of the principal component regression model is proposed for obtaining a fixed set of atomic charges (referred to as dipole-derived charges) optimized for reproducing the dipole moment of a conformationally rich molecule, i.e., a molecule with multiple local minima on the potential energy surface. The method does not require any adjustable parameters and requires the geometries of conformers, their dipole moments and atomic polar tensor (APT) charges as the only input data. The fixed atomic charges generated by the method not only reproduce the molecular dipole moment in all the conformers accurately, but are also numerically close to the APT charges, thereby ensuring accurate reproduction of the dipole moment variations caused by small geometrical distortions (e.g., by vibrations) of the conformers. The proposed method has been applied to canonical 2'-deoxyribonucleotides, the model DNA monomers, and the dipole-derived charges have been shown to outperform both the averaged APT and RESP charges in reproducing the dipole moments of large sets of conformers, thus demonstrating a potential usefulness of the dipole-derived charges as a 'reference point' for modeling polarization effects in conformationally rich molecules.
[Mh] Termos MeSH primário: Desoxirribonucleotídeos/química
[Mh] Termos MeSH secundário: Modelos Moleculares
Conformação Molecular
Teoria Quântica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Deoxyribonucleotides)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1039/c7cp05703b


  2 / 3141 MEDLINE  
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[PMID]:28457755
[Au] Autor:Kitamura Y; Asakura R; Terazawa K; Shibata A; Ikeda M; Kitade Y
[Ad] Endereço:Department of Biomolecular Science, Graduate School of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
[Ti] Título:Nucleobase azide-ethynylribose click chemistry contributes to stabilizing oligonucleotide duplexes and stem-loop structures.
[So] Source:Bioorg Med Chem Lett;27(12):2655-2658, 2017 06 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The formation of 1,4-disubstituted 1,2,3-triazoles through copper-catalyzed azide-alkyne cycloaddition (CuAAC) in oligonucleotides bearing 1-deoxy-1-ethynyl-ß-d-ribofuranose (R ) can have a positive impact on the stability of oligonucleotide duplexes and stem-loop structures.
[Mh] Termos MeSH primário: Azidas/química
Desoxirribonucleotídeos/química
Triazóis/síntese química
[Mh] Termos MeSH secundário: Catálise
Química Click
Cobre/química
Reação de Cicloadição
Estrutura Molecular
Triazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Azides); 0 (Deoxyribonucleotides); 0 (Triazoles); 789U1901C5 (Copper)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171124
[Lr] Data última revisão:
171124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:28911097
[Au] Autor:Moon AF; Pryor JM; Ramsden DA; Kunkel TA; Bebenek K; Pedersen LC
[Ad] Endereço:Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
[Ti] Título:Structural accommodation of ribonucleotide incorporation by the DNA repair enzyme polymerase Mu.
[So] Source:Nucleic Acids Res;45(15):9138-9148, 2017 Sep 06.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:While most DNA polymerases discriminate against ribonucleotide triphosphate (rNTP) incorporation very effectively, the Family X member DNA polymerase µ (Pol µ) incorporates rNTPs almost as efficiently as deoxyribonucleotides. To gain insight into how this occurs, here we have used X-ray crystallography to describe the structures of pre- and post-catalytic complexes of Pol µ with a ribonucleotide bound at the active site. These structures reveal that Pol µ binds and incorporates a rNTP with normal active site geometry and no distortion of the DNA substrate or nucleotide. Moreover, a comparison of rNTP incorporation kinetics by wildtype and mutant Pol µ indicates that rNTP accommodation involves synergistic interactions with multiple active site residues not found in polymerases with greater discrimination. Together, the results are consistent with the hypothesis that rNTP incorporation by Pol µ is advantageous in gap-filling synthesis during DNA double strand break repair by nonhomologous end joining, particularly in nonreplicating cells containing very low deoxyribonucleotide concentrations.
[Mh] Termos MeSH primário: Reparo do DNA por Junção de Extremidades
DNA Polimerase Dirigida por DNA/química
DNA/química
Desoxirribonucleotídeos/química
Ribonucleotídeos/química
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Sequência de Bases
Domínio Catalítico
Clonagem Molecular
Cristalografia por Raios X
DNA/metabolismo
DNA Polimerase Dirigida por DNA/genética
DNA Polimerase Dirigida por DNA/metabolismo
Desoxirribonucleotídeos/metabolismo
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Seres Humanos
Cinética
Modelos Moleculares
Conformação de Ácido Nucleico
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Domínios e Motivos de Interação entre Proteínas
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Ribonucleotídeos/metabolismo
Especificidade por Substrato
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Deoxyribonucleotides); 0 (Recombinant Proteins); 0 (Ribonucleotides); 9007-49-2 (DNA); EC 2.7.7.- (DNA polymerase mu); EC 2.7.7.7 (DNA-Directed DNA Polymerase)
[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:170916
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx527


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[PMID]:28862868
[Au] Autor:Alnajjar KS; Negahbani A; Nakhjiri M; Krylov IS; Kashemirov BA; McKenna CE; Goodman MF; Sweasy JB
[Ad] Endereço:Department of Therapeutic Radiology and Department of Genetics, Yale University School of Medicine , New Haven, Connecticut 06520, United States.
[Ti] Título:DNA Polymerase ß Cancer-Associated Variant I260M Exhibits Nonspecific Selectivity toward the ß-γ Bridging Group of the Incoming dNTP.
[So] Source:Biochemistry;56(40):5449-5456, 2017 Oct 10.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The hydrophobic hinge region of DNA polymerase ß (pol ß) is located between the fingers and palm subdomains. The hydrophobicity of the hinge region is important for maintaining the geometry of the binding pocket and for the selectivity of the enzyme. Various cancer-associated pol ß variants in the hinge region have reduced fidelity resulting from a decreased discrimination at the level of dNTP binding. Specifically, I260M, a prostate cancer-associated variant of pol ß, has been shown to have a reduced discrimination during dNTP binding and also during nucleotidyl transfer. To test whether fidelity of the I260M variant is dependent on leaving group chemistry, we employed a toolkit comprising dNTP bisphosphonate analogues modified at the ß-γ bridging methylene to modulate leaving group (pCXYp mimicking PP ) basicity. Construction of linear free energy relationship plots for the dependence of log(k ) on leaving group pK revealed that I260M catalyzes dNMP incorporation with a marked negative dependence on leaving group basicity, consistent with a chemical transition state, during both correct and incorrect incorporation. Additionally, we provide evidence that I260M fidelity is altered in the presence of some of the analogues, possibly resulting from a lack of coordination between the fingers and palm subdomains in the presence of the I260M mutation.
[Mh] Termos MeSH primário: DNA Polimerase beta/genética
DNA Polimerase beta/metabolismo
Desoxirribonucleotídeos/química
Desoxirribonucleotídeos/metabolismo
Mutação
Neoplasias/genética
[Mh] Termos MeSH secundário: DNA Polimerase beta/química
Cinética
Modelos Moleculares
Neoplasias/enzimologia
Ligação Proteica
Conformação Proteica
Especificidade por Substrato
Nucleotídeos de Timina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Deoxyribonucleotides); 0 (Thymine Nucleotides); EC 2.7.7.- (DNA Polymerase beta); QOP4K539MU (thymidine 5'-triphosphate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170902
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00713


  5 / 3141 MEDLINE  
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[PMID]:28735680
[Au] Autor:Song Y; Marmion RA; Park JO; Biswas D; Rabinowitz JD; Shvartsman SY
[Ad] Endereço:The Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
[Ti] Título:Dynamic Control of dNTP Synthesis in Early Embryos.
[So] Source:Dev Cell;42(3):301-308.e3, 2017 Aug 07.
[Is] ISSN:1878-1551
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Exponential increase of cell numbers in early embryos requires large amounts of DNA precursors (deoxyribonucleoside triphosphates (dNTPs)). Little is understood about how embryos satisfy this demand. We examined dNTP metabolism in the early Drosophila embryo, in which gastrulation is preceded by 13 sequential nuclear cleavages within only 2 hr of fertilization. Surprisingly, despite the breakneck speed at which Drosophila embryos synthesize DNA, maternally deposited dNTPs can generate less than half of the genomes needed to reach gastrulation. The rest of the dNTPs are synthesized "on the go." The rate-limiting enzyme of dNTP synthesis, ribonucleotide reductase, is inhibited by endogenous levels of deoxyATP (dATP) present at fertilization and is activated as dATP is depleted via DNA polymerization. This feedback inhibition renders the concentration of dNTPs at gastrulation robust, with respect to large variations in maternal supplies, and is essential for normal progression of embryogenesis.
[Mh] Termos MeSH primário: Desoxirribonucleotídeos/metabolismo
Drosophila/metabolismo
Retroalimentação Fisiológica
[Mh] Termos MeSH secundário: Animais
Desoxirribonucleotídeos/biossíntese
Drosophila/embriologia
Drosophila/genética
Desenvolvimento Embrionário
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Deoxyribonucleotides)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170725
[St] Status:MEDLINE


  6 / 3141 MEDLINE  
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[PMID]:28714480
[Au] Autor:Técher H; Koundrioukoff S; Nicolas A; Debatisse M
[Ad] Endereço:IFOM, the FIRC institute of Molecular Oncology, DNA metabolism laboratory, Via Adamello 16, 20139 Milan, Italy.
[Ti] Título:The impact of replication stress on replication dynamics and DNA damage in vertebrate cells.
[So] Source:Nat Rev Genet;18(9):535-550, 2017 Sep.
[Is] ISSN:1471-0064
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The interplay between replication stress and the S phase checkpoint is a key determinant of genome maintenance, and has a major impact on human diseases, notably, tumour initiation and progression. Recent studies have yielded insights into sequence-dependent and sequence-independent sources of endogenous replication stress. These stresses result in nuclease-induced DNA damage, checkpoint activation and genome-wide replication fork slowing. Several hypotheses have been proposed to account for the mechanisms involved in this complex response. Recent results have shown that the slowing of the replication forks most commonly results from DNA precursor starvation. By concomitantly increasing the density of replication initiation, the cell elicits an efficient compensatory strategy to avoid mitotic anomalies and the inheritance of damage over cell generations.
[Mh] Termos MeSH primário: Dano ao DNA
Replicação do DNA
[Mh] Termos MeSH secundário: Animais
Ciclo Celular
Células/metabolismo
Desoxirribonucleotídeos/metabolismo
Seres Humanos
Conformação de Ácido Nucleico
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Deoxyribonucleotides)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170818
[Lr] Data última revisão:
170818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE
[do] DOI:10.1038/nrg.2017.46


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[PMID]:28686433
[Au] Autor:Xiao Y; Liu Q; Tang X; Yang Z; Wu L; He Y
[Ad] Endereço:School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences , Beijing 100049, China.
[Ti] Título:Mirror-Image Thymidine Discriminates against Incorporation of Deoxyribonucleotide Triphosphate into DNA and Repairs Itself by DNA Polymerases.
[So] Source:Bioconjug Chem;28(8):2125-2134, 2017 Aug 16.
[Is] ISSN:1520-4812
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:DNA polymerases are known to recognize preferably d-nucleotides over l-nucleotides during DNA synthesis. Here, we report that several general DNA polymerases catalyze polymerization reactions of nucleotides directed by the DNA template containing an l-thymidine (l-T). The results display that the 5'-3' primer extension of natural nucleotides get to the end at chiral modification site with Taq and Phanta Max DNA polymerases, but the primer extension proceeds to the end of the template catalyzed by Deep Vent (exo ), Vent (exo ), and Therminator DNA polymerases. Furthermore, templating l-nucleoside displays a lag in the deoxyribonucleotide triphosphate (dNTP) incorporation rates relative to natural template by kinetics analysis, and polymerase chain reactions were inhibited with the DNA template containing two or three consecutive l-Ts. Most interestingly, no single base mutation or mismatch mixture corresponding to the location of l-T in the template was found, which is physiologically significant because they provide a theoretical basis on the involvement of DNA polymerase in the effective repair of l-T that may lead to cytotoxicity.
[Mh] Termos MeSH primário: Reparo do DNA
DNA Polimerase Dirigida por DNA/metabolismo
DNA/química
DNA/metabolismo
Desoxirribonucleotídeos/metabolismo
Timidina/metabolismo
[Mh] Termos MeSH secundário: Pareamento de Bases
Sequência de Bases
DNA/biossíntese
DNA/genética
Replicação do DNA
Cinética
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Deoxyribonucleotides); 9007-49-2 (DNA); EC 2.7.7.7 (DNA-Directed DNA Polymerase); VC2W18DGKR (Thymidine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.1021/acs.bioconjchem.7b00301


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[PMID]:28604743
[Au] Autor:Garzón J; Rodríguez R; Kong Z; Chabes A; Rodríguez-Acebes S; Méndez J; Moreno S; García-Higuera I
[Ad] Endereço:Instituto de Biología Funcional y Genómica (IBFG)-CSIC, Salamanca University, Salamanca, Spain.
[Ti] Título:Shortage of dNTPs underlies altered replication dynamics and DNA breakage in the absence of the APC/C cofactor Cdh1.
[So] Source:Oncogene;36(42):5808-5818, 2017 Oct 19.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The APC/C-Cdh1 ubiquitin-ligase complex targets cell cycle regulators for proteosomal degradation and helps prevent tumor development and accumulation of chromosomal aberrations. Replication stress has been proposed to be the main driver of genomic instability in the absence of Cdh1, but the real contribution of APC/C-Cdh1 to efficient replication, especially in normal cells, remains unclear. Here we show that, in primary MEFs, acute depletion or permanent ablation of Cdh1 slowed down replication fork movement and increased origin activity. Partial inhibition of origin firing does not accelerate replication forks, suggesting that fork progression is intrinsically limited in the absence of Cdh1. Moreover, exogenous supply of nucleotide precursors, or ectopic overexpression of RRM2, the regulatory subunit of Ribonucleotide Reductase, restore replication efficiency, indicating that dNTP availability could be impaired upon Cdh1 loss. Indeed, we found reduced dNTP levels in Cdh1-deficient MEFs. Importantly, DNA breakage is also significantly alleviated by increasing intracellular dNTP pools, strongly suggesting that genomic instability is the result of aberrant replication. These observations highlight the relevance of APC/C-Cdh1 activity during G1 to ensure an adequate supply of dNTPs to the replisome, prevent replication stress and the resulting chromosomal breaks and, ultimately, suppress tumorigenesis.
[Mh] Termos MeSH primário: Ciclossomo-Complexo Promotor de Anáfase/metabolismo
Proteínas Cdh1/fisiologia
Quebras de DNA
Replicação do DNA
Desoxirribonucleotídeos/metabolismo
Fase G1
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Embrião de Mamíferos/citologia
Embrião de Mamíferos/metabolismo
Feminino
Fibroblastos/citologia
Fibroblastos/metabolismo
Instabilidade Genômica
Masculino
Camundongos
Camundongos Knockout
Ribonucleosídeo Difosfato Redutase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cdh1 Proteins); 0 (Deoxyribonucleotides); 0 (Fzr1 protein, mouse); EC 1.17.4.- (ribonucleotide reductase M2); EC 1.17.4.1 (Ribonucleoside Diphosphate Reductase); EC 2.3.2.27 (Anaphase-Promoting Complex-Cyclosome)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2017.186


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[PMID]:28335578
[Au] Autor:Li Z; Guo JR; Chen QQ; Wang CY; Zhang WJ; Yao MC; Zhang W
[Ad] Endereço:State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, China. lizhengcpu@163.com.
[Ti] Título:Exploring the Antitumor Mechanism of High-Dose Cytarabine through the Metabolic Perturbations of Ribonucleotide and Deoxyribonucleotide in Human Promyelocytic Leukemia HL-60 Cells.
[So] Source:Molecules;22(3), 2017 Mar 21.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Despite the apparent clinical benefits of high-dose cytarabine (Ara-C) over lower dose Ara-C in acute myeloid leukemia (AML) therapy, the mechanism behind high-dose Ara-C therapy remains uncertain. In this study, a LC-MS-based method was carried out to investigate the metabolic alteration of ribonucleotide and deoxyribonucleotide in human promyelocytic leukemia cells (HL-60) after treatment with Ara-C to reveal its antitumor mechanism. The metabolic results revealed that four nucleotides (ATP, ADP, CDP, and dCTP) could be used as potential biomarkers indicating the benefit of high-dose Ara-C over lower dose Ara-C treatment. Combining metabolic perturbation and cell cycle analysis, we conjectured that, apart from the acknowledged mechanism of Ara-C on tumor inhibition, high-dose Ara-C could present a specific action pathway. It was suggested that the pronounced rise in AMP/ATP ratio induced by high-dose Ara-C can trigger AMP-activated protein kinase (AMPK) and subsequently Forkhead Box, class O (FoxO), to promote cell cycle arrest. Moreover, the significant decrease in CDP pool induced by high-dose Ara-C might further accelerate the reduction of dCTP, which then aggravates DNA synthesis disturbance. As a result, all of these alterations led to heightened tumor inhibition. This study provides new insight in the investigation of potential mechanisms in the clinical benefits of high-dose Ara-C in therapy for AML.
[Mh] Termos MeSH primário: Antimetabólitos Antineoplásicos/farmacologia
Citarabina/farmacologia
Desoxirribonucleotídeos/análise
Ribonucleotídeos/análise
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/metabolismo
Ciclo Celular/efeitos dos fármacos
Cromatografia Gasosa-Espectrometria de Massas
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Células HL-60
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimetabolites, Antineoplastic); 0 (Deoxyribonucleotides); 0 (Ribonucleotides); 04079A1RDZ (Cytarabine); EC 2.7.11.31 (AMP-Activated Protein Kinases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE


  10 / 3141 MEDLINE  
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[PMID]:28180291
[Au] Autor:Kochenova OV; Bezalel-Buch R; Tran P; Makarova AV; Chabes A; Burgers PM; Shcherbakova PV
[Ad] Endereço:Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
[Ti] Título:Yeast DNA polymerase ζ maintains consistent activity and mutagenicity across a wide range of physiological dNTP concentrations.
[So] Source:Nucleic Acids Res;45(3):1200-1218, 2017 02 17.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In yeast, dNTP pools expand drastically during DNA damage response. We show that similar dNTP elevation occurs in strains, in which intrinsic replisome defects promote the participation of error-prone DNA polymerase ζ (Polζ) in replication of undamaged DNA. To understand the significance of dNTP pools increase for Polζ function, we studied the activity and fidelity of four-subunit Polζ (Polζ4) and Polζ4-Rev1 (Polζ5) complexes in vitro at 'normal S-phase' and 'damage-response' dNTP concentrations. The presence of Rev1 inhibited the activity of Polζ and greatly increased the rate of all three 'X-dCTP' mispairs, which Polζ4 alone made extremely inefficiently. Both Polζ4 and Polζ5 were most promiscuous at G nucleotides and frequently generated multiple closely spaced sequence changes. Surprisingly, the shift from 'S-phase' to 'damage-response' dNTP levels only minimally affected the activity, fidelity and error specificity of Polζ complexes. Moreover, Polζ-dependent mutagenesis triggered by replisome defects or UV irradiation in vivo was not decreased when dNTP synthesis was suppressed by hydroxyurea, indicating that Polζ function does not require high dNTP levels. The results support a model wherein dNTP elevation is needed to facilitate non-mutagenic tolerance pathways, while Polζ synthesis represents a unique mechanism of rescuing stalled replication when dNTP supply is low.
[Mh] Termos MeSH primário: Desoxirribonucleotídeos/metabolismo
Proteínas de Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/enzimologia
Saccharomyces cerevisiae/genética
[Mh] Termos MeSH secundário: Dano ao DNA
Replicação do DNA
DNA Fúngico/genética
DNA Fúngico/metabolismo
DNA Polimerase Dirigida por DNA/química
DNA Polimerase Dirigida por DNA/genética
DNA Polimerase Dirigida por DNA/metabolismo
Mutagênese
Nucleotidiltransferases/química
Nucleotidiltransferases/genética
Nucleotidiltransferases/metabolismo
Subunidades Proteicas
Proteínas de Saccharomyces cerevisiae/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA, Fungal); 0 (Deoxyribonucleotides); 0 (Protein Subunits); 0 (Saccharomyces cerevisiae Proteins); 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:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170210
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkw1149



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