Base de dados : MEDLINE
Pesquisa : A11.284.430.106.279.345.190.160 [Categoria DeCS]
Referências encontradas : 155 [refinar]
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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]:29196537
[Au] Autor:Kawasumi R; Abe T; Arakawa H; Garre M; Hirota K; Branzei D
[Ad] Endereço:The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology (IFOM), 20139 Milan, Italy.
[Ti] Título:ESCO1/2's roles in chromosome structure and interphase chromatin organization.
[So] Source:Genes Dev;31(21):2136-2150, 2017 11 01.
[Is] ISSN:1549-5477
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:ESCO1/2 acetyltransferases mediating SMC3 acetylation and sister chromatid cohesion (SCC) are differentially required for genome integrity and development. Here we established chicken DT40 cell lines with mutations in ESCO1/2, SMC3 acetylation, and the cohesin remover WAPL. Both ESCO1 and ESCO2 promoted SCC, while ESCO2 was additionally and specifically required for proliferation and centromere integrity. overexpression fully suppressed the slow proliferation and centromeric separation phenotypes of cells but only partly suppressed its chromosome arm SCC defects. Concomitant inactivation of ESCO1 and ESCO2 caused lethality owing to compromised mitotic chromosome segregation. Neither nor acetyl-mimicking mutations rescued lethality. Notably, conditional mutants showed very severe proliferation defects associated with catastrophic mitoses and also abnormal interphase chromatin organization patterns. The results indicate that cohesion establishment by vertebrate ESCO1/2 is linked to interphase chromatin architecture formation, a newly identified function of cohesin acetyltransferases that is both fundamentally and medically relevant.
[Mh] Termos MeSH primário: Acetiltransferases/metabolismo
Montagem e Desmontagem da Cromatina/genética
Proteínas Cromossômicas não Histona/metabolismo
Estruturas Cromossômicas/genética
Instabilidade Genômica/genética
[Mh] Termos MeSH secundário: Acetilação
Acetiltransferases/genética
Animais
Linhagem Celular
Proliferação Celular/genética
Centrômero/genética
Galinhas
Proteínas Cromossômicas não Histona/genética
Técnicas de Inativação de Genes
Inativação Gênica
Interfase/genética
Proteínas Nucleares/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chromosomal Proteins, Non-Histone); 0 (Nuclear Proteins); EC 2.3.1.- (Acetyltransferases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171203
[St] Status:MEDLINE
[do] DOI:10.1101/gad.306084.117


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[PMID]:28825700
[Au] Autor:Schalbetter SA; Goloborodko A; Fudenberg G; Belton JM; Miles C; Yu M; Dekker J; Mirny L; Baxter J
[Ad] Endereço:Genome Damage and Stability Centre, Science Park Road, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
[Ti] Título:SMC complexes differentially compact mitotic chromosomes according to genomic context.
[So] Source:Nat Cell Biol;19(9):1071-1080, 2017 Sep.
[Is] ISSN:1476-4679
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Structural maintenance of chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids, while condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate that this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead, it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes.
[Mh] Termos MeSH primário: Adenosina Trifosfatases/metabolismo
Proteínas de Ciclo Celular/metabolismo
Montagem e Desmontagem da Cromatina
Cromatina/metabolismo
Proteínas Cromossômicas não Histona/metabolismo
Estruturas Cromossômicas
Cromossomos Fúngicos/metabolismo
DNA Fúngico/metabolismo
Proteínas de Ligação a DNA/metabolismo
Mitose
Complexos Multiproteicos/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/metabolismo
[Mh] Termos MeSH secundário: Adenosina Trifosfatases/genética
Proteínas de Ciclo Celular/genética
Cromatina/química
Cromatina/genética
Proteínas Cromossômicas não Histona/genética
Cromossomos Fúngicos/química
Cromossomos Fúngicos/genética
Simulação por Computador
DNA Fúngico/química
DNA Fúngico/genética
DNA Ribossômico/química
DNA Ribossômico/genética
DNA Ribossômico/metabolismo
Proteínas de Ligação a DNA/genética
Modelos Genéticos
Modelos Moleculares
Complexos Multiproteicos/genética
Conformação de Ácido Nucleico
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/crescimento & desenvolvimento
Proteínas de Saccharomyces cerevisiae/genética
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Chromatin); 0 (Chromosomal Proteins, Non-Histone); 0 (DNA, Fungal); 0 (DNA, Ribosomal); 0 (DNA-Binding Proteins); 0 (Multiprotein Complexes); 0 (Saccharomyces cerevisiae Proteins); 0 (cohesins); 0 (condensin complexes); EC 3.6.1.- (Adenosine Triphosphatases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170822
[St] Status:MEDLINE
[do] DOI:10.1038/ncb3594


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[PMID]:28704368
[Au] Autor:Arbogast T; Iacono G; Chevalier C; Afinowi NO; Houbaert X; van Eede MC; Laliberte C; Birling MC; Linda K; Meziane H; Selloum M; Sorg T; Nadif Kasri N; Koolen DA; Stunnenberg HG; Henkelman RM; Kopanitsa M; Humeau Y; De Vries BBA; Herault Y
[Ad] Endereço:Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg, Illkirch, France.
[Ti] Título:Mouse models of 17q21.31 microdeletion and microduplication syndromes highlight the importance of Kansl1 for cognition.
[So] Source:PLoS Genet;13(7):e1006886, 2017 Jul.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Koolen-de Vries syndrome (KdVS) is a multi-system disorder characterized by intellectual disability, friendly behavior, and congenital malformations. The syndrome is caused either by microdeletions in the 17q21.31 chromosomal region or by variants in the KANSL1 gene. The reciprocal 17q21.31 microduplication syndrome is associated with psychomotor delay, and reduced social interaction. To investigate the pathophysiology of 17q21.31 microdeletion and microduplication syndromes, we generated three mouse models: 1) the deletion (Del/+); or 2) the reciprocal duplication (Dup/+) of the 17q21.31 syntenic region; and 3) a heterozygous Kansl1 (Kans1+/-) model. We found altered weight, general activity, social behaviors, object recognition, and fear conditioning memory associated with craniofacial and brain structural changes observed in both Del/+ and Dup/+ animals. By investigating hippocampus function, we showed synaptic transmission defects in Del/+ and Dup/+ mice. Mutant mice with a heterozygous loss-of-function mutation in Kansl1 displayed similar behavioral and anatomical phenotypes compared to Del/+ mice with the exception of sociability phenotypes. Genes controlling chromatin organization, synaptic transmission and neurogenesis were upregulated in the hippocampus of Del/+ and Kansl1+/- animals. Our results demonstrate the implication of KANSL1 in the manifestation of KdVS phenotypes and extend substantially our knowledge about biological processes affected by these mutations. Clear differences in social behavior and gene expression profiles between Del/+ and Kansl1+/- mice suggested potential roles of other genes affected by the 17q21.31 deletion. Together, these novel mouse models provide new genetic tools valuable for the development of therapeutic approaches.
[Mh] Termos MeSH primário: Anormalidades Múltiplas/genética
Duplicação Cromossômica/genética
Cognição
Deficiência Intelectual/genética
Proteínas Nucleares/genética
[Mh] Termos MeSH secundário: Animais
Peso Corporal
Encéfalo/metabolismo
Encéfalo/ultraestrutura
Deleção Cromossômica
Estruturas Cromossômicas/genética
Estruturas Cromossômicas/metabolismo
Cromossomos Humanos Par 17/genética
Variações do Número de Cópias de DNA
Modelos Animais de Doenças
Epigênese Genética
Feminino
Deleção de Genes
Rearranjo Gênico
Hipocampo/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Plasticidade Neuronal/genética
Proteínas Nucleares/metabolismo
Transmissão Sináptica/genética
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (KANSL1 protein, mouse); 0 (Nuclear Proteins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170714
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006886


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[PMID]:28238318
[Au] Autor:Viot G; Jacquemard F
[Ad] Endereço:Centre pluridiciplinaire de diagnostic Prénatal, hôpital américain de Paris, 63, boulevard Victor-Hugo, 92200 Neuilly-sur-Seine, France.
[Ti] Título:[Answer to the article by F. Vialrd et al.: Does the prevalence of recurrent pathogenic microdeletions and microdoublements in prenatal diagnosis lead to a reassessment of the evolution of non-invasive screening techniques? The example of region 22q11.2].
[Ti] Título:Réponse à l'article de F. Vialard et al. : la prévalence des microdélétions et microduplications pathogènes récurrentes en diagnostic prénatal doit-elle amener à revoir l'évolution des techniques de dépistage non invasif ? L'exemple de la région 22q11.2..
[So] Source:Gynecol Obstet Fertil Senol;45(1):50-53, 2017 01.
[Is] ISSN:2468-7189
[Cp] País de publicação:France
[La] Idioma:fre
[Mh] Termos MeSH primário: Deleção Cromossômica
Diagnóstico Pré-Natal
[Mh] Termos MeSH secundário: Estruturas Cromossômicas
Cromossomos Humanos Par 22
Hibridização Genômica Comparativa
Síndrome de DiGeorge
Feminino
Cardiopatias Congênitas
Seres Humanos
Hibridização in Situ Fluorescente
Fenótipo
Gravidez
Prevalência
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170228
[St] Status:MEDLINE


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[PMID]:28193284
[Au] Autor:Valenzuela CY
[Ad] Endereço:Programa de Genética Humana, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia 1027, Casilla 70061, Independencia, Chile. cvalenzu@med.uchile.cl.
[Ti] Título:Selective intra-dinucleotide interactions and periodicities of bases separated by K sites: a new vision and tool for phylogeny analyses.
[So] Source:Biol Res;50(1):3, 2017 Feb 13.
[Is] ISSN:0717-6287
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Direct tests of the random or non-random distribution of nucleotides on genomes have been devised to test the hypothesis of neutral, nearly-neutral or selective evolution. These tests are based on the direct base distribution and are independent of the functional (coding or non-coding) or structural (repeated or unique sequences) properties of the DNA. The first approach described the longitudinal distribution of bases in tandem repeats under the Bose-Einstein statistics. A huge deviation from randomness was found. A second approach was the study of the base distribution within dinucleotides whose bases were separated by 0, 1, 2… K nucleotides. Again an enormous difference from the random distribution was found with significances out of tables and programs. These test values were periodical and included the 16 dinucleotides. For example a high "positive" (more observed than expected dinucleotides) value, found in dinucleotides whose bases were separated by (3K + 2) sites, was preceded by two smaller "negative" (less observed than expected dinucleotides) values, whose bases were separated by (3K) or (3K + 1) sites. We examined mtDNAs, prokaryote genomes and some eukaryote chromosomes and found that the significant non-random interactions and periodicities were present up to 1000 or more sites of base separation and in human chromosome 21 until separations of more than 10 millions sites. Each nucleotide has its own significant value of its distance to neutrality; this yields 16 hierarchical significances. A three dimensional table with the number of sites of separation between the bases and the 16 significances (the third dimension is the dinucleotide, individual or taxon involved) gives directly an evolutionary state of the analyzed genome that can be used to obtain phylogenies. An example is provided.
[Mh] Termos MeSH primário: Sequência de Bases/genética
Genoma
Nucleotídeos/genética
Filogenia
Análise de Sequência de DNA/métodos
[Mh] Termos MeSH secundário: Algoritmos
Animais
Distribuição de Qui-Quadrado
Estruturas Cromossômicas
Colágeno/genética
DNA Mitocondrial/genética
Drosophila melanogaster/genética
Epistasia Genética/genética
Evolução Molecular
Deriva Genética
HIV-1/genética
Seres Humanos
Nucleotídeos/química
Periodicidade
Células Procarióticas/química
Valores de Referência
Sequências de Repetição em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Mitochondrial); 0 (Nucleotides); 9007-34-5 (Collagen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170810
[Lr] Data última revisão:
170810
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170215
[St] Status:MEDLINE
[do] DOI:10.1186/s40659-017-0112-0


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[PMID]:27807046
[Au] Autor:Matheson TD; Kaufman PD
[Ad] Endereço:Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605.
[Ti] Título:The p150N domain of chromatin assembly factor-1 regulates Ki-67 accumulation on the mitotic perichromosomal layer.
[So] Source:Mol Biol Cell;28(1):21-29, 2017 Jan 01.
[Is] ISSN:1939-4586
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chromatin assembly factor 1 (CAF-1) deposits histones during DNA synthesis. The p150 subunit of human CAF-1 contains an N-terminal domain (p150N) that is dispensable for histone deposition but promotes the localization of specific loci (nucleolar-associated domains [NADs]) and proteins to the nucleolus during interphase. One of the p150N-regulated proteins is proliferation antigen Ki-67, whose depletion also decreases the nucleolar association of NADs. Ki-67 is also a fundamental component of the perichromosomal layer (PCL), a sheath of proteins surrounding condensed chromosomes during mitosis. We show here that a subset of p150 localizes to the PCL during mitosis and that p150N is required for normal levels of Ki-67 accumulation on the PCL. This activity requires the sumoylation-interacting motif within p150N, which is also required for the nucleolar localization of NADs and Ki-67 during interphase. In this manner, p150N coordinates both interphase and mitotic nuclear structures via Ki67.
[Mh] Termos MeSH primário: Fator 1 de Modelagem da Cromatina/metabolismo
Antígeno Ki-67/metabolismo
[Mh] Termos MeSH secundário: Ciclo Celular/fisiologia
Nucléolo Celular/metabolismo
Cromatina/metabolismo
Fator 1 de Modelagem da Cromatina/genética
Estruturas Cromossômicas/metabolismo
Cromossomos/metabolismo
Células HeLa
Histonas/genética
Histonas/metabolismo
Seres Humanos
Interfase/fisiologia
Antígeno Ki-67/genética
Mitose/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CHAF1A protein, human); 0 (Chromatin); 0 (Chromatin Assembly Factor-1); 0 (Histones); 0 (Ki-67 Antigen)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161104
[St] Status:MEDLINE
[do] DOI:10.1091/mbc.E16-09-0659


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[PMID]:27821047
[Au] Autor:Adhikari B; Trieu T; Cheng J
[Ad] Endereço:Computer Science Department, University of Missouri, Columbia, MO, 65211, USA.
[Ti] Título:Chromosome3D: reconstructing three-dimensional chromosomal structures from Hi-C interaction frequency data using distance geometry simulated annealing.
[So] Source:BMC Genomics;17(1):886, 2016 11 07.
[Is] ISSN:1471-2164
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Reconstructing three-dimensional structures of chromosomes is useful for visualizing their shapes in a cell and interpreting their function. In this work, we reconstruct chromosomal structures from Hi-C data by translating contact counts in Hi-C data into Euclidean distances between chromosomal regions and then satisfying these distances using a structure reconstruction method rigorously tested in the field of protein structure determination. RESULTS: We first evaluate the robustness of the overall reconstruction algorithm on noisy simulated data at various levels of noise by comparing with some of the state-of-the-art reconstruction methods. Then, using simulated data, we validate that Spearman's rank correlation coefficient between pairwise distances in the reconstructed chromosomal structures and the experimental chromosomal contact counts can be used to find optimum conversion rules for transforming interaction frequencies to wish distances. This strategy is then applied to real Hi-C data at chromosome level for optimal transformation of interaction frequencies to wish distances and for ranking and selecting structures. The chromosomal structures reconstructed from a real-world human Hi-C dataset by our method were validated by the known two-compartment feature of the human chromosome organization. We also show that our method is robust with respect to the change of the granularity of Hi-C data, and consistently produces similar structures at different chromosomal resolutions. CONCLUSION: Chromosome3D is a robust method of reconstructing chromosome three-dimensional models using distance restraints obtained from Hi-C interaction frequency data. It is available as a web application and as an open source tool at http://sysbio.rnet.missouri.edu/chromosome3d/ .
[Mh] Termos MeSH primário: Estruturas Cromossômicas/química
Imagem Tridimensional
Modelos Moleculares
Conformação de Ácido Nucleico
[Mh] Termos MeSH secundário: Algoritmos
Simulação por Computador
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171119
[Lr] Data última revisão:
171119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161109
[St] Status:MEDLINE


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[PMID]:27737961
[Au] Autor:Woodward J; Taylor GC; Soares DC; Boyle S; Sie D; Read D; Chathoth K; Vukovic M; Tarrats N; Jamieson D; Campbell KJ; Blyth K; Acosta JC; Ylstra B; Arends MJ; Kranc KR; Jackson AP; Bickmore WA; Wood AJ
[Ad] Endereço:MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom.
[Ti] Título:Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability.
[So] Source:Genes Dev;30(19):2173-2186, 2016 Oct 01.
[Is] ISSN:1549-5477
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chromosomal instability is a hallmark of cancer, but mitotic regulators are rarely mutated in tumors. Mutations in the condensin complexes, which restructure chromosomes to facilitate segregation during mitosis, are significantly enriched in cancer genomes, but experimental evidence implicating condensin dysfunction in tumorigenesis is lacking. We report that mice inheriting missense mutations in a condensin II subunit (Caph2 ) develop T-cell lymphoma. Before tumors develop, we found that the same Caph2 mutation impairs ploidy maintenance to a different extent in different hematopoietic cell types, with ploidy most severely perturbed at the CD4 CD8 T-cell stage from which tumors initiate. Premalignant CD4 CD8 T cells show persistent catenations during chromosome segregation, triggering DNA damage in diploid daughter cells and elevated ploidy. Genome sequencing revealed that Caph2 single-mutant tumors are near diploid but carry deletions spanning tumor suppressor genes, whereas P53 inactivation allowed Caph2 mutant cells with whole-chromosome gains and structural rearrangements to form highly aggressive disease. Together, our data challenge the view that mitotic chromosome formation is an invariant process during development and provide evidence that defective mitotic chromosome structure can promote tumorigenesis.
[Mh] Termos MeSH primário: Adenosina Trifosfatases/genética
Proteínas de Ligação a DNA/genética
Instabilidade Genômica/genética
Linfoma de Células T/genética
Complexos Multiproteicos/genética
Mutação de Sentido Incorreto/genética
Neoplasias do Timo/genética
[Mh] Termos MeSH secundário: Adenosina Trifosfatases/metabolismo
Anáfase
Animais
Células Cultivadas
Estruturas Cromossômicas/genética
Proteínas de Ligação a DNA/metabolismo
Feminino
Linfoma de Células T/fisiopatologia
Masculino
Metáfase
Camundongos
Complexos Multiproteicos/metabolismo
Timócitos/patologia
Neoplasias do Timo/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (Multiprotein Complexes); 0 (condensin complexes); EC 3.6.1.- (Adenosine Triphosphatases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161015
[St] Status:MEDLINE


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[PMID]:27504668
[Au] Autor:Ohta S; Kimura M; Takagi S; Toramoto I; Ishihama Y
[Ad] Endereço:Center for Innovative and Translational Medicine Medical School, Kochi University Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan.
[Ti] Título:Identification of Mitosis-Specific Phosphorylation in Mitotic Chromosome-Associated Proteins.
[So] Source:J Proteome Res;15(9):3331-41, 2016 Sep 02.
[Is] ISSN:1535-3907
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During mitosis, phosphorylation of chromosome-associated proteins is a key regulatory mechanism. Mass spectrometry has been successfully applied to determine the complete protein composition of mitotic chromosomes, but not to identify post-translational modifications. Here, we quantitatively compared the phosphoproteome of isolated mitotic chromosomes with that of chromosomes in nonsynchronized cells. We identified 4274 total phosphorylation sites and 350 mitosis-specific phosphorylation sites in mitotic chromosome-associated proteins. Significant mitosis-specific phosphorylation in centromere/kinetochore proteins was detected, although the chromosomal association of these proteins did not change throughout the cell cycle. This mitosis-specific phosphorylation might play a key role in regulation of mitosis. Further analysis revealed strong dependency of phosphorylation dynamics on kinase consensus patterns, thus linking the identified phosphorylation sites to known key mitotic kinases. Remarkably, chromosomal axial proteins such as non-SMC subunits of condensin, TopoIIα, and Kif4A, together with the chromosomal periphery protein Ki67 involved in the establishment of the mitotic chromosomal structure, demonstrated high phosphorylation during mitosis. These findings suggest a novel mechanism for regulation of chromosome restructuring in mitosis via protein phosphorylation. Our study generated a large quantitative database on protein phosphorylation in mitotic and nonmitotic chromosomes, thus providing insights into the dynamics of chromatin protein phosphorylation at mitosis onset.
[Mh] Termos MeSH primário: Proteínas Cromossômicas não Histona/metabolismo
Mitose
[Mh] Termos MeSH secundário: Sítios de Ligação
Linhagem Celular
Estruturas Cromossômicas
Seres Humanos
Fosforilação
Proteínas Quinases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromosomal Proteins, Non-Histone); EC 2.7.- (Protein Kinases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160810
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jproteome.6b00512



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