16 results on '"Alain Verreault"'
Search Results
2. Chromatin dynamics and DNA replication roadblocks
- Author
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Alain Verreault, Hugo Wurtele, and Ian Hammond-Martel
- Subjects
DNA Replication ,DNA Repair ,DNA damage ,DNA repair ,Biochemistry ,Chromatin Assembly ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Humans ,Nascent dna ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,biology ,DNA replication ,Eukaryota ,DNA ,Cell Biology ,Chromatin Assembly and Disassembly ,Chromatin ,Cell biology ,Histone Code ,Histone ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,DNA Damage - Abstract
A broad spectrum of spontaneous and genotoxin-induced DNA lesions impede replication fork progression. The DNA damage response that acts to promote completion of DNA replication is associated with dynamic changes in chromatin structure that include two distinct processes which operate genome-wide during S-phase. The first, often referred to as histone recycling or parental histone segregation, is characterized by the transfer of parental histones located ahead of replication forks onto nascent DNA. The second, known as de novo chromatin assembly, consists of the deposition of new histone molecules onto nascent DNA. Because these two processes occur at all replication forks, their potential to influence a multitude of DNA repair and DNA damage tolerance mechanisms is considerable. The purpose of this review is to provide a description of parental histone segregation and de novo chromatin assembly, and to illustrate how these processes influence cellular responses to DNA replication roadblocks.
- Published
- 2021
3. Acetylation of PCNA Sliding Surface by Eco1 Promotes Genome Stability through Homologous Recombination
- Author
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Jean-François Couture, Alain Verreault, Joseph S. Brunzelle, Anne-Claude Gingras, Jean-Philippe Lambert, Jacques Côté, Pierre Billon, Véronique Tremblay, Jian Li, Tomohiko Sugiyama, and Yizhang Chen
- Subjects
Models, Molecular ,0301 basic medicine ,Saccharomyces cerevisiae Proteins ,Genotype ,Protein Conformation ,DNA repair ,DNA damage ,Saccharomyces cerevisiae ,Chromatids ,Genomic Instability ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Acetyltransferases ,Proliferating Cell Nuclear Antigen ,Humans ,Molecular Biology ,DNA Polymerase III ,DNA clamp ,030102 biochemistry & molecular biology ,biology ,Lysine ,DNA replication ,Nuclear Proteins ,Recombinational DNA Repair ,Acetylation ,Cell Biology ,Molecular biology ,Proliferating cell nuclear antigen ,Cell biology ,Phenotype ,030104 developmental biology ,chemistry ,Mutation ,biology.protein ,DNA mismatch repair ,Chromosomes, Fungal ,Homologous recombination ,Protein Processing, Post-Translational ,DNA ,DNA Damage - Abstract
During DNA replication, proliferating cell nuclear antigen (PCNA) adopts a ring-shaped structure to promote processive DNA synthesis, acting as a sliding clamp for polymerases. Known posttranslational modifications function at the outer surface of the PCNA ring to favor DNA damage bypass. Here, we demonstrate that acetylation of lysine residues at the inner surface of PCNA is induced by DNA lesions. We show that cohesin acetyltransferase Eco1 targets lysine 20 at the sliding surface of the PCNA ring in vitro and in vivo in response to DNA damage. Mimicking constitutive acetylation stimulates homologous recombination and robustly suppresses the DNA damage sensitivity of mutations in damage tolerance pathways. In comparison to the unmodified trimer, structural differences are observed at the interface between protomers in the crystal structure of the PCNA-K20ac ring. Thus, acetylation regulates PCNA sliding on DNA in the presence of DNA damage, favoring homologous recombination linked to sister-chromatid cohesion.
- Published
- 2017
4. Regulation of the Histone Deacetylase Hst3 by Cyclin-dependent Kinases and the Ubiquitin Ligase SCFCdc4
- Author
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Pierre Thibault, Xiaojing Tang, Mike Tyers, Evgeny Kanshin, Alain Verreault, Elizabeth C. Williams, Neda Delgoshaie, and Adam D. Rudner
- Subjects
Saccharomyces cerevisiae Proteins ,Ubiquitin-Protein Ligases ,Cell Cycle Proteins ,Saccharomyces cerevisiae ,DNA and Chromosomes ,Biochemistry ,Histone Deacetylases ,Histones ,Histone H3 ,Cyclin-dependent kinase ,Enzyme Stability ,Phosphorylation ,Molecular Biology ,Cyclin-dependent kinase 1 ,biology ,F-Box Proteins ,Cell Cycle ,Ubiquitination ,Acetylation ,Cell Biology ,Cell cycle ,HDAC4 ,Ubiquitin ligase ,biology.protein ,Histone deacetylase ,Genome, Fungal - Abstract
In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56ac) is a modification of new H3 molecules deposited throughout the genome during S-phase. H3K56ac is removed by the sirtuins Hst3 and Hst4 at later stages of the cell cycle. Previous studies indicated that regulated degradation of Hst3 plays an important role in the genome-wide waves of H3K56 acetylation and deacetylation that occur during each cell cycle. However, little is known regarding the mechanism of cell cycle-regulated Hst3 degradation. Here, we demonstrate that Hst3 instability in vivo is dependent upon the ubiquitin ligase SCF(Cdc4) and that Hst3 is phosphorylated at two Cdk1 sites, threonine 380 and threonine 384. This creates a diphosphorylated degron that is necessary for Hst3 polyubiquitylation by SCF(Cdc4). Mutation of the Hst3 diphospho-degron does not completely stabilize Hst3 in vivo, but it nonetheless results in a significant fitness defect that is particularly severe in mutant cells treated with the alkylating agent methyl methanesulfonate. Unexpectedly, we show that Hst3 can be degraded between G2 and anaphase, a window of the cell cycle where Hst3 normally mediates genome-wide deacetylation of H3K56. Our results suggest an intricate coordination between Hst3 synthesis, genome-wide H3K56 deacetylation by Hst3, and cell cycle-regulated degradation of Hst3 by cyclin-dependent kinases and SCF(Cdc4).
- Published
- 2014
5. The dual function of LMO2 in driving erythroid cell fate
- Author
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Véronique Lisi, Alain Verreault, François Major, Magali Humbert, Diogo F.T. Veiga, Trang Hoang, Marie-Claude Sincennes, and Bachir Affar
- Subjects
LMO2 ,Cancer Research ,Chemistry ,Genetics ,Erythroid cell ,Cell Biology ,Hematology ,Molecular Biology ,Dual function ,Cell biology - Published
- 2017
6. Structure of the Rtt109-AcCoA/Vps75 Complex and Implications for Chaperone-Mediated Histone Acetylation
- Author
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Katrina Meeth, Marc A. Holbert, Paul Drogaris, Alain Verreault, Ronen Marmorstein, Pierre Thibault, Hugo Wurtele, Yong Tang, Hua Yuan, Neda Delgoshaie, Benoit Guillemette, Eun Hye Lee, Philip A. Cole, and Chantal Durette
- Subjects
Models, Molecular ,Saccharomyces cerevisiae Proteins ,Nucleosome assembly ,Recombinant Fusion Proteins ,Saccharomyces cerevisiae ,Gene Expression ,Cell Cycle Proteins ,Plasma protein binding ,Crystallography, X-Ray ,Genomic Instability ,Article ,Substrate Specificity ,Histones ,03 medical and health sciences ,Histone H3 ,0302 clinical medicine ,Acetyl Coenzyme A ,Structural Biology ,Humans ,Molecular Biology ,Histone Acetyltransferases ,030304 developmental biology ,0303 health sciences ,biology ,Lysine ,Acetylation ,Chromatin Assembly and Disassembly ,biology.organism_classification ,3. Good health ,Cell biology ,Histone ,Biochemistry ,Chaperone (protein) ,Mutagenesis, Site-Directed ,biology.protein ,030217 neurology & neurosurgery ,Molecular Chaperones ,Protein Binding - Abstract
SummaryYeast Rtt109 promotes nucleosome assembly and genome stability by acetylating K9, K27, and K56 of histone H3 through interaction with either of two distinct histone chaperones, Vps75 or Asf1. We report the crystal structure of an Rtt109-AcCoA/Vps75 complex revealing an elongated Vps75 homodimer bound to two globular Rtt109 molecules to form a symmetrical holoenzyme with a ∼12 Å diameter central hole. Vps75 and Rtt109 residues that mediate complex formation in the crystals are also important for Rtt109-Vps75 interaction and H3K9/K27 acetylation both in vitro and in yeast cells. The same Rtt109 residues do not participate in Asf1-mediated Rtt109 acetylation in vitro or H3K56 acetylation in yeast cells, demonstrating that Asf1 and Vps75 dictate Rtt109 substrate specificity through distinct mechanisms. These studies also suggest that Vps75 binding stimulates Rtt109 catalytic activity by appropriately presenting the H3-H4 substrate within the central cavity of the holoenzyme to promote H3K9/K27 acetylation of new histones before deposition.
- Published
- 2011
7. Artifactual Sulfation of Silver-stained Proteins
- Author
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Mathieu Courcelles, Alain Verreault, Sylvain Meloche, Maria Marcantonio, Pierre Thibault, Marlene Gharib, and Sylvia G. Lehmann
- Subjects
Gel electrophoresis ,Thiosulfate ,Chemistry ,Biochemistry ,Analytical Chemistry ,Staining ,Silver stain ,chemistry.chemical_compound ,Sulfation ,Phosphorylation ,Threonine ,Tyrosine ,Molecular Biology - Abstract
Sulfation and phosphorylation are post-translational modifications imparting an isobaric 80-Da addition on the side chain of serine, threonine, or tyrosine residues. These two post-translational modifications are often difficult to distinguish because of their similar MS fragmentation patterns. Targeted MS identification of these modifications in specific proteins commonly relies on their prior separation using gel electrophoresis and silver staining. In the present investigation, we report a potential pitfall in the interpretation of these modifications from silver-stained gels due to artifactual sulfation of serine, threonine, and tyrosine residues by sodium thiosulfate, a commonly used reagent that catalyzes the formation of metallic silver deposits onto proteins. Detailed MS analyses of gel-separated protein standards and Escherichia coli cell extracts indicated that several serine, threonine, and tyrosine residues were sulfated using silver staining protocols but not following Coomassie Blue staining. Sodium thiosulfate was identified as the reagent leading to this unexpected side reaction, and the degree of sulfation was correlated with increasing concentrations of thiosulfate up to 0.02%, which is typically used for silver staining. The significance of this artifact is discussed in the broader context of sulfation and phosphorylation site identification from in vivo and in vitro experiments.
- Published
- 2009
8. Structural Basis for the Recognition of Histone H4 by the Histone-Chaperone RbAp46
- Author
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Wei Zhang, Ernest D. Laue, Natalia V. Murzina, Tom Rolef Ben-Shahar, Alain Verreault, Stephen H. McLaughlin, J. Venkatesh Pratap, Jose Vicente-Garcia, Xue-Yuan Pei, Mike Sparkes, and Ben F. Luisi
- Subjects
Models, Molecular ,PROTEINS ,Molecular Sequence Data ,Biology ,Article ,Histone H4 ,Histones ,03 medical and health sciences ,Histone H3 ,0302 clinical medicine ,Histone H1 ,Structural Biology ,Histone H2A ,Histone methylation ,Histone code ,Humans ,Histone octamer ,Amino Acid Sequence ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Binding Sites ,Sequence Homology, Amino Acid ,Nuclear Proteins ,DNA ,Cell biology ,Biochemistry ,Histone methyltransferase ,Retinoblastoma-Binding Protein 7 ,Carrier Proteins ,030217 neurology & neurosurgery ,Molecular Chaperones ,Protein Binding - Abstract
Summary RbAp46 and RbAp48 (pRB-associated proteins p46 and p48, also known as RBBP7 and RBBP4, respectively) are highly homologous histone chaperones that play key roles in establishing and maintaining chromatin structure. We report here the crystal structure of human RbAp46 bound to histone H4. RbAp46 folds into a seven-bladed β propeller structure and binds histone H4 in a groove formed between an N-terminal α helix and an extended loop inserted into blade six. Surprisingly, histone H4 adopts a different conformation when interacting with RbAp46 than it does in either the nucleosome or in the complex with ASF1, another histone chaperone. Our structural and biochemical results suggest that when a histone H3/H4 dimer (or tetramer) binds to RbAp46 or RbAp48, helix 1 of histone H4 unfolds to interact with the histone chaperone. We discuss the implications of our findings for the assembly and function of RbAp46 and RbAp48 complexes.
- Published
- 2008
- Full Text
- View/download PDF
9. Regulation of Histone H3 Lysine 56 Acetylation in Schizosaccharomyces pombe
- Author
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Hiroshi Masumoto, Stephen P. Jackson, Alain Verreault, Kyle M. Miller, Blerta Xhemalce, Tony Kouzarides, Benoit Arcangioli, and Robert Driscoll
- Subjects
DNA Replication ,G2 Phase ,Saccharomyces cerevisiae Proteins ,SAP30 ,Biochemistry ,S Phase ,Histones ,Histone H3 ,Histone H1 ,Schizosaccharomyces ,Histone H2A ,Histone code ,DNA Breaks, Double-Stranded ,Histone octamer ,Molecular Biology ,Histone Acetyltransferases ,Sequence Homology, Amino Acid ,biology ,Lysine ,Acetylation ,Cell Biology ,Histone acetyltransferase ,biology.protein ,Schizosaccharomyces pombe Proteins ,Histone deacetylase ,Protein Processing, Post-Translational ,Mutagens - Abstract
In Saccharomyces cerevisiae, acetylation of lysine 56 (Lys-56) in the globular domain of histone H3 plays an important role in response to genotoxic agents that interfere with DNA replication. However, the regulation and biological function of this modification are poorly defined in other eukaryotes. Here we show that Lys-56 acetylation in Schizosaccharomyces pombe occurs transiently during passage through S-phase and is normally removed in G(2). Genotoxic agents that cause DNA double strand breaks during replication elicit a delay in deacetylation of histone H3 Lys-56. In addition, mutant cells that cannot acetylate Lys-56 are acutely sensitive to genotoxic agents that block DNA replication. Moreover, we show that Spbc342.06cp, a previously uncharacterized open reading frame, encodes the functional homolog of S. cerevisiae Rtt109, and that this protein acetylates H3 Lys-56 both in vitro and in vivo. Altogether, our results indicate that both the regulation of histone H3 Lys-56 acetylation by its histone acetyltransferase and histone deacetylase and its role in the DNA damage response are conserved among two distantly related yeast model organisms.
- Published
- 2007
10. The emergence of regulated histone proteolysis
- Author
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Johanna Paik, Alain Verreault, and Akash Gunjan
- Subjects
Histone deacetylase 5 ,biology ,Hydrolysis ,Genetic Variation ,DNA ,Models, Biological ,Histones ,Histone ,Gene Expression Regulation ,Biochemistry ,Histone H1 ,Histone methyltransferase ,Histone methylation ,Histone H2A ,Genetics ,biology.protein ,Animals ,Humans ,Nucleosome ,Histone code ,Developmental Biology - Abstract
Proliferating cells need to synthesize large amounts of histones to rapidly package nascent DNA into nucleosomes. This is a challenging task for cells because changes in rates of DNA synthesis lead to an accumulation of excess histones, which interfere with many aspects of DNA metabolism. In addition, cells need to ensure that histone variants are incorporated at the correct chromosomal location. Recent discoveries have highlighted the importance of regulated histone proteolysis in preventing both the accumulation of excess histones and the mis-incorporation of histone variants at inappropriate loci.
- Published
- 2006
11. Histone H3 Lysine 4 Mono-methylation does not Require Ubiquitination of Histone H2B
- Author
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Ramon Sendra, Daniéle Moinier, Mercè Pamblanco, Pierre Luciano, Pierre-Marie Dehé, Alain Verreault, Vincent Géli, Régine Lebrun, and Vicente Tordera
- Subjects
Histone H3 Lysine 4 ,Ubiquitin ,Lysine ,Saccharomyces cerevisiae ,Biology ,Methylation ,environment and public health ,Molecular biology ,Cell biology ,Histones ,Histone H1 ,Structural Biology ,Histone methyltransferase ,Histone H2A ,Histone methylation ,Histone H2B ,Histone code ,Histone octamer ,Molecular Biology - Abstract
The yeast Set1-complex catalyzes histone H3 lysine 4 (H3K4) methylation. Using N-terminal Edman sequencing, we determined that 50% of H3K4 is methylated and consists of roughly equal amounts of mono, di and tri-methylated H3K4. We further show that loss of either Paf1 of the Paf1 elongation complex, or ubiquitination of histone H2B, has only a modest effect on bulk histone mono-methylation at H3K4. Despite the fact that Set1 recruitment decreases in paf1delta cells, loss of Paf1 results in an increase of H3K4 mono-methylation at the 5' coding region of active genes, suggesting a Paf1-independent targeting of Set1. In contrast to Paf1 inactivation, deleting RTF1 affects H3K4 mono-methylation at the 3' coding region of active genes and results in a decrease of global H3K4 mono-methylation. Our results indicate that the requirements for mono-methylation are distinct from those for H3K4 di and tri-methylation, and point to differences among members of the Paf1 complex in the regulation of H3K4 methylation.
- Published
- 2005
12. Heterochromatin Dynamics in Mouse Cells
- Author
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Natalia V. Murzina, Bruce Stillman, Ernest D. Laue, and Alain Verreault
- Subjects
endocrine system ,animal structures ,Nucleosome assembly ,Cell Biology ,Solenoid (DNA) ,Biology ,Chromatin ,Cell biology ,Non-histone protein ,embryonic structures ,Histone code ,Nucleosome ,Heterochromatin protein 1 ,Chromatin Assembly Factor-1 ,Molecular Biology - Abstract
Mechanisms contributing to the maintenance of heterochromatin in proliferating cells are poorly understood. We demonstrate that chromatin assembly factor 1 (CAF-1) binds to mouse HP1 proteins via an N-terminal domain of its p150 subunit, a domain dispensable for nucleosome assembly during DNA replication. Mutations in p150 prevent association with HP1 in heterochromatin in cells that are not in S phase and the formation of CAF-1-HP1 complexes in nascent chromatin during DNA replication in vitro. We suggest that CAF-1 p150 has a heterochromatin-specific function distinct from its nucleosome assembly function during S phase. Just before mitosis, CAF-1 p150 and some HP1 progressively dissociate from heterochromatin concomitant with histone H3 phosphorylation. The HP1 proteins reassociate with chromatin at the end of mitosis, as histone H3 is dephosphorylated.
- Published
- 1999
13. Nucleosome Assembly by a Complex of CAF-1 and Acetylated Histones H3/H4
- Author
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Paul D. Kaufman, Bruce Stillman, Alain Verreault, and Ryuji Kobayashi
- Subjects
Cell Extracts ,DNA Replication ,Cytoplasm ,DNA, Complementary ,Saccharomyces cerevisiae Proteins ,Nucleosome assembly ,Chromosomal Proteins, Non-Histone ,Molecular Sequence Data ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Histones ,Histone H4 ,Histone H1 ,Acetyltransferases ,Histone H2A ,Humans ,Histone code ,Amino Acid Sequence ,Histone octamer ,Chromatin Assembly Factor-1 ,Cloning, Molecular ,Histone Acetyltransferases ,Cell Nucleus ,Biochemistry, Genetics and Molecular Biology(all) ,Lysine ,Chromatin Assembly Factor I ,Acetylation ,Molecular biology ,Chromatin ,Nucleosomes ,Cell biology ,DNA-Binding Proteins ,Molecular Weight ,Transcription Factors - Abstract
Chromatin assembly factor 1 (CAF-1) assembles nucleosomes in a replication-dependent manner. The small subunit of CAF-1 (p48) is a member of a highly conserved subfamily of WD-repeat proteins. There are at least two members of this subfamily in both human (p46 and p48) and yeast cells (Hat2p, a subunit of the B-type H4 acetyltransferase, and Msi1p). Human p48 can bind to histone H4 in the absence of CAF-1 p150 and p60. p48, also a known subunit of a histone deacetylase, copurifies with a chromatin assembly complex (CAC), which contains the three subunits of CAF-1 (p150, p60, p48) and H3 and H4, and promotes DNA replication-dependent chromatin assembly. CAC histone H4 exhibits a novel pattern of lysine acetylation that overlaps with, but is distinct from, that reported for newly synthesized H4 isolated from nascent chromatin. Our data suggest that CAC is a key intermediate of the de novo nucleosome assembly pathway and that the p48 subunit participates in other aspects of histone metabolism.
- Published
- 1996
14. Biochemical properties and function of poly(ADP-ribose) glycohydrolase
- Author
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J.C. Hoflack, S. Desnoyers, Alain Verreault, G.M. Shah, G.G. Poirier, and G. Brochu
- Subjects
Cell Nucleus ,chemistry.chemical_classification ,PARG ,DNA Repair ,Glycoside Hydrolases ,Poly ADP ribose polymerase ,General Medicine ,Biochemistry ,Isoenzymes ,Structure-Activity Relationship ,chemistry.chemical_compound ,Enzyme ,Monomer ,chemistry ,Covalent bond ,Animals ,Humans ,NAD+ kinase ,Polyacrylamide gel electrophoresis ,Poly(ADP-ribose) glycohydrolase - Abstract
We describe here the latest observations on poly(ADP-ribose) glycohydrolase. There is now extensive evidence that this nuclear enzyme is an endo-exoglycosidase which has a key role to perform in the removal of polymers which interact with proteins through covalent and non-covalent interactions. Also, we have developed a zymogram which will permit the isolation of the various isoforms of the glycohydrolase and the eventual cloning of this enzyme. Finally, we have evidence that very short oligomers and even monomers of ADP-ribose covalently bound to proteins can be removed by poly(ADP-ribose) glycohydrolase.
- Published
- 1995
15. LMO1/2 regulates DNA replication in hematopoietic cells
- Author
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Benoit Grondin, Magali Humbert, Alain Verreault, Mathieu Tremblay, Marie-Claude Sincennes, André Haman, and Trang Hoang
- Subjects
DNA replication factor CDT1 ,Cancer Research ,Haematopoiesis ,biology ,Control of chromosome duplication ,Genetics ,DNA replication ,biology.protein ,Eukaryotic DNA replication ,Cell Biology ,Hematology ,Molecular Biology ,Cell biology - Published
- 2014
16. Histone Deposition at the Replication Fork
- Author
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Alain Verreault
- Subjects
Genetics ,Nucleosome assembly ,Control of chromosome duplication ,Histone H2A ,Histone code ,Origin recognition complex ,Eukaryotic DNA replication ,Cell Biology ,Biology ,Pre-replication complex ,Molecular Biology ,S phase ,Cell biology - Abstract
In this issue of Molecular Cell, Ye et al. provide a biological rationale for rapid histone deposition behind the replication fork. They show that defects in nucleosome assembly lead to DNA double-strand breaks and S phase arrest. Their results have important implications for the maintenance of genome integrity in proliferating cells.
- Published
- 2003
- Full Text
- View/download PDF
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