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[PMID]:29408272
[Au] Autor:Saif I; Kasmi Y; Allali K; Ennaji MM
[Ad] Endereço:Team of Virology, Oncology and Medical Biotechnologies, Laboratory of Virology, Microbiology, Quality and Biotechnologies/ETB, Faculty of Science sand Technologies-Mohammedia, Hassan II University of Casablanca, Morocco.
[Ti] Título:Prediction of DNA methylation in the promoter of gene suppressor tumor.
[So] Source:Gene;651:166-173, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The epigenetics methylation of cytosine is the most common epigenetic form in DNA sequences. It is highly concentrated in the promoter regions of the genes, leading to an inactivation of tumor suppressors regardless of their initial function. In this work, we aim to identify the highly methylated regions; the cytosine-phosphate-guanine (CpG) island located on the promoters and/or the first exon gene known for their key roles in the cell cycle, hence the need to study gene-gene interactions. The Frommer and hidden Markov model algorithms are used as computational methods to identify CpG islands with specificity and sensitivity up to 76% and 80%, respectively. The results obtained show, on the one hand, that the genes studied are suspected of developing hypermethylation in the promoter region of the gene involved in the case of a cancer. We then showed that the relative richness in CG results from a high level of methylation. On the other hand, we observe that the gene-gene interaction exhibits co-expression between the chosen genes. This let us to conclude that the hidden Markov model algorithm predicts more specific and valuable information about the hypermethylation in gene as a preventive and diagnostics tools for the personalized medicine; as that the tumor-suppresser-genes have relative co-expression and complementary relations which the hypermethylation affect in the samples studied in our work.
[Mh] Termos MeSH primário: Biologia Computacional/métodos
Ilhas de CpG
Metilação de DNA
Genes Supressores de Tumor
Regiões Promotoras Genéticas
[Mh] Termos MeSH secundário: Algoritmos
DNA de Neoplasias
Conjuntos de Dados como Assunto
Epistasia Genética
Seres Humanos
Cadeias de Markov
Modelos Genéticos
Neoplasias/genética
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Neoplasm)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


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[PMID]:29202706
[Au] Autor:Li J; Zeng W; Zhang Y; Ko AM; Li C; Zhu H; Fu Q; Zhou H
[Ad] Endereço:College of Life Science, Jilin University, Changchun, 130023, People's Republic of China.
[Ti] Título:Ancient DNA reveals genetic connections between early Di-Qiang and Han Chinese.
[So] Source:BMC Evol Biol;17(1):239, 2017 Dec 04.
[Is] ISSN:1471-2148
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Ancient Di-Qiang people once resided in the Ganqing region of China, adjacent to the Central Plain area from where Han Chinese originated. While gene flow between the Di-Qiang and Han Chinese has been proposed, there is no evidence to support this view. Here we analyzed the human remains from an early Di-Qiang site (Mogou site dated ~4000 years old) and compared them to other ancient DNA across China, including an early Han-related site (Hengbei site dated ~3000 years old) to establish the underlying genetic relationship between the Di-Qiang and ancestors of Han Chinese. RESULTS: We found Mogou mtDNA haplogroups were highly diverse, comprising 14 haplogroups: A, B, C, D (D*, D4, D5), F, G, M7, M8, M10, M13, M25, N*, N9a, and Z. In contrast, Mogou males were all Y-DNA haplogroup O3a2/P201; specifically one male was further assigned to O3a2c1a/M117 using targeted unique regions on the non-recombining region of the Y-chromosome. We compared Mogou to 7 other ancient and 38 modern Chinese groups, in a total of 1793 individuals, and found that Mogou shared close genetic distances with Taojiazhai (a more recent Di-Qiang population), Hengbei, and Northern Han. We modeled their interactions using Approximate Bayesian Computation, and support was given to a potential admixture of ~13-18% between the Mogou and Northern Han around 3300-3800 years ago. CONCLUSIONS: Mogou harbors the earliest genetically identifiable Di-Qiang, ancestral to the Taojiazhai, and up to ~33% paternal and ~70% of its maternal haplogroups could be found in present-day Northern Han Chinese.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
DNA Antigo
Grupos Étnicos/genética
[Mh] Termos MeSH secundário: Teorema de Bayes
China
Cromossomos Humanos Y/genética
Simulação por Computador
DNA Mitocondrial/genética
Genética Populacional
Geografia
Haplótipos/genética
Seres Humanos
Masculino
Modelos Genéticos
Filogenia
Polimorfismo de Nucleotídeo Único/genética
Análise de Componente Principal
Probabilidade
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Ancient); 0 (DNA, Mitochondrial)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1186/s12862-017-1082-0


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[PMID]:29286779
[Au] Autor:Chuang HM; Reifenberger JG; Cao H; Dorfman KD
[Ad] Endereço:Department of Chemical Engineering and Materials Science, University of Minnesota-Twin Cities, 421 Washington Avenue SE, Minneapolis, Minnesota 55455, USA.
[Ti] Título:Sequence-Dependent Persistence Length of Long DNA.
[So] Source:Phys Rev Lett;119(22):227802, 2017 Dec 01.
[Is] ISSN:1079-7114
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Using a high-throughput genome-mapping approach, we obtained circa 50 million measurements of the extension of internal human DNA segments in a 41 nm×41 nm nanochannel. The underlying DNA sequences, obtained by mapping to the reference human genome, are 2.5-393 kilobase pairs long and contain percent GC contents between 32.5% and 60%. Using Odijk's theory for a channel-confined wormlike chain, these data reveal that the DNA persistence length increases by almost 20% as the percent GC content increases. The increased persistence length is rationalized by a model, containing no adjustable parameters, that treats the DNA as a statistical terpolymer with a sequence-dependent intrinsic persistence length and a sequence-independent electrostatic persistence length.
[Mh] Termos MeSH primário: DNA/química
DNA/genética
Modelos Químicos
Modelos Genéticos
[Mh] Termos MeSH secundário: Sequência de Bases
Sequenciamento de Nucleotídeos em Larga Escala/métodos
Seres Humanos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9007-49-2 (DNA)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171230
[St] Status:MEDLINE
[do] DOI:10.1103/PhysRevLett.119.227802


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[PMID]:29212445
[Au] Autor:Lyubetsky V; Gershgorin R; Gorbunov K
[Ad] Endereço:Institute for Information Transmission Problems of the Russian Academy of Sciences (Kharkevich Institute), Bolshoy Karetny per. 19, build.1, Moscow, 127051, Russia.
[Ti] Título:Chromosome structures: reduction of certain problems with unequal gene content and gene paralogs to integer linear programming.
[So] Source:BMC Bioinformatics;18(1):537, 2017 Dec 06.
[Is] ISSN:1471-2105
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Chromosome structure is a very limited model of the genome including the information about its chromosomes such as their linear or circular organization, the order of genes on them, and the DNA strand encoding a gene. Gene lengths, nucleotide composition, and intergenic regions are ignored. Although highly incomplete, such structure can be used in many cases, e.g., to reconstruct phylogeny and evolutionary events, to identify gene synteny, regulatory elements and promoters (considering highly conserved elements), etc. Three problems are considered; all assume unequal gene content and the presence of gene paralogs. The distance problem is to determine the minimum number of operations required to transform one chromosome structure into another and the corresponding transformation itself including the identification of paralogs in two structures. We use the DCJ model which is one of the most studied combinatorial rearrangement models. Double-, sesqui-, and single-operations as well as deletion and insertion of a chromosome region are considered in the model; the single ones comprise cut and join. In the reconstruction problem, a phylogenetic tree with chromosome structures in the leaves is given. It is necessary to assign the structures to inner nodes of the tree to minimize the sum of distances between terminal structures of each edge and to identify the mutual paralogs in a fairly large set of structures. A linear algorithm is known for the distance problem without paralogs, while the presence of paralogs makes it NP-hard. If paralogs are allowed but the insertion and deletion operations are missing (and special constraints are imposed), the reduction of the distance problem to integer linear programming is known. Apparently, the reconstruction problem is NP-hard even in the absence of paralogs. The problem of contigs is to find the optimal arrangements for each given set of contigs, which also includes the mutual identification of paralogs. RESULTS: We proved that these problems can be reduced to integer linear programming formulations, which allows an algorithm to redefine the problems to implement a very special case of the integer linear programming tool. The results were tested on synthetic and biological samples. CONCLUSIONS: Three well-known problems were reduced to a very special case of integer linear programming, which is a new method of their solutions. Integer linear programming is clearly among the main computational methods and, as generally accepted, is fast on average; in particular, computation systems specifically targeted at it are available. The challenges are to reduce the size of the corresponding integer linear programming formulations and to incorporate a more detailed biological concept in our model of the reconstruction.
[Mh] Termos MeSH primário: Estruturas Cromossômicas
Genoma
Modelos Genéticos
Programação Linear
[Mh] Termos MeSH secundário: Evolução Biológica
Biologia Computacional
Filogenia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1186/s12859-017-1944-x


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[PMID]:28453670
[Au] Autor:Adams RH; Schield DR; Card DC; Blackmon H; Castoe TA
[Ad] Endereço:Department of Biology, The University of Texas at Arlington, Arlington, TX 76019, USA.
[Ti] Título:GppFst: genomic posterior predictive simulations of FST and dXY for identifying outlier loci from population genomic data.
[So] Source:Bioinformatics;33(9):1414-1415, 2017 May 01.
[Is] ISSN:1367-4811
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Summary: We introduce GppFst, an open source R package that generates posterior predictive distributions of FST and dx under a neutral coalescent model to identify putative targets of selection from genomic data. Availability and Implementation: GppFst is available at ( https://github.com/radamsRHA/GppFst ). Contact: todd.castoe@uta.edu. Supplementary information: Supplementary data are available at Bioinformatics online.
[Mh] Termos MeSH primário: Loci Gênicos
Genética Populacional/métodos
Modelos Genéticos
Polimorfismo de Nucleotídeo Único
Software
[Mh] Termos MeSH secundário: Algoritmos
Animais
Crotalus/genética
Genoma
Genômica/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/bioinformatics/btw795


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[PMID]:28453671
[Au] Autor:Krukov I; de Sanctis B; de Koning APJ
[Ad] Endereço:Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
[Ti] Título:Wright-Fisher exact solver (WFES): scalable analysis of population genetic models without simulation or diffusion theory.
[So] Source:Bioinformatics;33(9):1416-1417, 2017 May 01.
[Is] ISSN:1367-4811
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Motivation: The simplifying assumptions that are used widely in theoretical population genetics may not always be appropriate for empirical population genetics. General computational approaches that do not require the assumptions of classical theory are therefore quite desirable. One such general approach is provided by the theory of absorbing Markov chains, which can be used to obtain exact results by directly analyzing population genetic Markov models, such as the classic bi-allelic Wright-Fisher model. Although these approaches are sometimes used, they are usually forgone in favor of simulation methods, due to the perception that they are too computationally burdensome. Here we show that, surprisingly, direct analysis of virtually any Markov chain model in population genetics can be made quite efficient by exploiting transition matrix sparsity and by solving restricted systems of linear equations, allowing a wide variety of exact calculations (within machine precision) to be easily and rapidly made on modern workstation computers. Results: We introduce Wright-Fisher Exact Solver (WFES), a fast and scalable method for direct analysis of Markov chain models in population genetics. WFES can rapidly solve for both long-term and transient behaviours including fixation and extinction probabilities, expected times to fixation or extinction, sojourn times, expected allele age and variance, and others. Our implementation requires only seconds to minutes of runtime on modern workstations and scales to biological population sizes ranging from humans to model organisms. Availability and Implementation: The code is available at https://github.com/dekoning-lab/wfes. Contact: jason.dekoning@ucalgary.ca. Supplementary information: Supplementary data are available at Bioinformatics online.
[Mh] Termos MeSH primário: Alelos
Genética Populacional/métodos
Modelos Genéticos
Software
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Cadeias de Markov
Densidade Demográfica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/bioinformatics/btw802


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[PMID]:29176784
[Au] Autor:Fu C; Heitman J
[Ad] Endereço:Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, United States of America.
[Ti] Título:PRM1 and KAR5 function in cell-cell fusion and karyogamy to drive distinct bisexual and unisexual cycles in the Cryptococcus pathogenic species complex.
[So] Source:PLoS Genet;13(11):e1007113, 2017 Nov.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sexual reproduction is critical for successful evolution of eukaryotic organisms in adaptation to changing environments. In the opportunistic human fungal pathogens, the Cryptococcus pathogenic species complex, C. neoformans primarily undergoes bisexual reproduction, while C. deneoformans undergoes both unisexual and bisexual reproduction. During both unisexual and bisexual cycles, a common set of genetic circuits regulates a yeast-to-hyphal morphological transition, that produces either monokaryotic or dikaryotic hyphae. As such, both the unisexual and bisexual cycles can generate genotypic and phenotypic diversity de novo. Despite the similarities between these two cycles, genetic and morphological differences exist, such as the absence of an opposite mating-type partner and monokaryotic instead of dikaryotic hyphae during C. deneoformans unisexual cycle. To better understand the similarities and differences between these modes of sexual reproduction, we focused on two cellular processes involved in sexual reproduction: cell-cell fusion and karyogamy. We identified orthologs of the plasma membrane fusion protein Prm1 and the nuclear membrane fusion protein Kar5 in both Cryptococcus species, and demonstrated their conserved roles in cell fusion and karyogamy during C. deneoformans α-α unisexual reproduction and C. deneoformans and C. neoformans a-α bisexual reproduction. Notably, karyogamy occurs inside the basidum during bisexual reproduction in C. neoformans, but often occurs earlier following cell fusion during bisexual reproduction in C. deneoformans. Characterization of these two genes also showed that cell fusion is dispensable for solo unisexual reproduction in C. deneoformans. The blastospores produced along hyphae during C. deneoformans unisexual reproduction are diploid, suggesting that diploidization occurs early during hyphal development, possibly through either an endoreplication pathway or cell fusion-independent karyogamy events. Taken together, our findings suggest distinct mating mechanisms for unisexual and bisexual reproduction in Cryptococcus, exemplifying distinct evolutionary trajectories within this pathogenic species complex.
[Mh] Termos MeSH primário: Cryptococcus neoformans/genética
Proteínas Fúngicas/genética
Genes Fúngicos Tipo Acasalamento/genética
Reprodução Assexuada/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Núcleo Celular/genética
Núcleo Celular/metabolismo
Cryptococcus neoformans/citologia
Cryptococcus neoformans/crescimento & desenvolvimento
Diploide
Regulação da Expressão Gênica no Desenvolvimento
Regulação Fúngica da Expressão Gênica
Hifas/genética
Hifas/crescimento & desenvolvimento
Fusão de Membrana/genética
Microscopia Confocal
Modelos Genéticos
Mutação
Homologia de Sequência de Aminoácidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fungal Proteins)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007113


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[PMID]:29302032
[Au] Autor:Mutlu A; Trauth S; Ziesack M; Nagler K; Bergeest JP; Rohr K; Becker N; Höfer T; Bischofs IB
[Ad] Endereço:BioQuant Center of the University of Heidelberg, 69120, Heidelberg, Germany.
[Ti] Título:Phenotypic memory in Bacillus subtilis links dormancy entry and exit by a spore quantity-quality tradeoff.
[So] Source:Nat Commun;9(1):69, 2018 01 04.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Some bacteria, such as Bacillus subtilis, withstand starvation by forming dormant spores that revive when nutrients become available. Although sporulation and spore revival jointly determine survival in fluctuating environments, the relationship between them has been unclear. Here we show that these two processes are linked by a phenotypic "memory" that arises from a carry-over of molecules from the vegetative cell into the spore. By imaging life histories of individual B. subtilis cells using fluorescent reporters, we demonstrate that sporulation timing controls nutrient-induced spore revival. Alanine dehydrogenase contributes to spore memory and controls alanine-induced outgrowth, thereby coupling a spore's revival capacity to the gene expression and growth history of its progenitors. A theoretical analysis, and experiments with signaling mutants exhibiting altered sporulation timing, support the hypothesis that such an intrinsically generated memory leads to a tradeoff between spore quantity and spore quality, which could drive the emergence of complex microbial traits.
[Mh] Termos MeSH primário: Bacillus subtilis/genética
Regulação Bacteriana da Expressão Gênica
Mutação
Esporos Bacterianos/genética
[Mh] Termos MeSH secundário: Alanina Desidrogenase/genética
Alanina Desidrogenase/metabolismo
Algoritmos
Bacillus subtilis/metabolismo
Bacillus subtilis/fisiologia
Fenômenos Fisiológicos Bacterianos/genética
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Modelos Genéticos
Esporos Bacterianos/crescimento & desenvolvimento
Esporos Bacterianos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); EC 1.4.1.1 (Alanine Dehydrogenase)
[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/s41467-017-02477-1


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[PMID]:29302024
[Au] Autor:Chen Y; Ho JML; Shis DL; Gupta C; Long J; Wagner DS; Ott W; Josic K; Bennett MR
[Ad] Endereço:Department of Biosciences, Rice University, 6100 Main Street, Houston, TX, 77005, USA.
[Ti] Título:Tuning the dynamic range of bacterial promoters regulated by ligand-inducible transcription factors.
[So] Source:Nat Commun;9(1):64, 2018 01 04.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:One challenge for synthetic biologists is the predictable tuning of genetic circuit regulatory components to elicit desired outputs. Gene expression driven by ligand-inducible transcription factor systems must exhibit the correct ON and OFF characteristics: appropriate activation and leakiness in the presence and absence of inducer, respectively. However, the dynamic range of a promoter (i.e., absolute difference between ON and OFF states) is difficult to control. We report a method that tunes the dynamic range of ligand-inducible promoters to achieve desired ON and OFF characteristics. We build combinatorial sets of AraC-and LasR-regulated promoters containing -10 and -35 sites from synthetic and Escherichia coli promoters. Four sequence combinations with diverse dynamic ranges were chosen to build multi-input transcriptional logic gates regulated by two and three ligand-inducible transcription factors (LacI, TetR, AraC, XylS, RhlR, LasR, and LuxR). This work enables predictable control over the dynamic range of regulatory components.
[Mh] Termos MeSH primário: Proteínas de Escherichia coli/genética
Escherichia coli/genética
Regulação Bacteriana da Expressão Gênica
Regiões Promotoras Genéticas/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Algoritmos
Escherichia coli/metabolismo
Proteínas de Escherichia coli/metabolismo
Ligantes
Modelos Genéticos
Termodinâmica
Fatores de Transcrição/metabolismo
Transcrição 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:
0 (Escherichia coli Proteins); 0 (Ligands); 0 (Transcription Factors)
[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/s41467-017-02473-5


  10 / 68078 MEDLINE  
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[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



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